Towards and understanding of nuclear morphogenesis

In the age of “virtual reality,” the imperfect microscopic silhouettes of cells and organelles are gradually being replaced by calligraphic computer drawings. In this context, textbooks and introductory slides often depict the cell nucleus as a smooth-shaped, featureless object. However, in reality, the nuclei of different cells possess distinct sizes and morphological features which develop in a programmed fashion as each cell differentiates. To dissect this complex morphogenetic process, we need to identify the basic elements that determine nuclear architecture and the regulatory factors involved. Recently, clues about the identity of these components have been obtained both by systematic analysis and by serendipity. This review summarizes a few recent findings and ideas that may serve as a first forum for future discussions and, I hope, for further work on this topic. © 1994 Wiley-Liss, Inc.     

A model of gradient interpretation based on morphogen binding

We propose a model in which pattern formation is controlled by several concentration gradients of “morphogens” and by allosteric proteins which bind them. In this model, each protein can bind up to two molecules of each morphogen and has an “active state” when one molecule of each morphogen is bound. The concentration of the active state of such a “morphogen binding protein” varies with position in a way that depends on the values given the binding constants. In a contour map of the active state concentration, the contours can have a variety of simple shapes.Simply-shaped regions of cell differentiation can be defined directly by concentration contours of a morphogen binding protein using a threshold-sensing mechanism. More complex shapes may be generated using several proteins and a “winner-take-all” rule according to which each protein specifies some particular sort of cell differentiation and the differentiation of cells in any position is governed by the protein with the highest active state concentration.We present an application of our model to the vertebrate limb skeleton; we use the “winner-take-all” mechanism and thirteen morphogen binding proteins, eleven of which specify cartilage formation. In this model we use one morphogen binding protein to specify the shaft of a typical long bone and one for each epiphysis. Our model is reasonably successful in imitating the in vivo positions and orientations of developing bones and in generating simple, plausible-looking articular surfaces.In addition to the morphogen-binding model we propose a mechanism which could transform morphogen-binding patterns into high-amplitude patterns capable of controlling the activity of structural genes. This “amplifying mechanism” can account for two previously unexplained features of limb skeletal development: the early formation of the diffusely-bounded “scleroblastema” in the limb bud and the center-to-edge gradations in cartilage formation rate which are later seen within individual chondrification foci.A simple modification of the morphogen-binding model provides an explanation for the general anatomical phenomenon of metamerism: The model can account for the formation of inexactly repeating patterns (such as the pattern of the vertebral column) and suggests a mechanism by which such patterns could (1) evolve from exactly repeating patterns, and (2) acquire, in further evolution, a high degree of specialization of the individual repeating units.The most promising approach for testing the morphogen-binding model would appear to involve experiments in which cytoplasm is transferred between cells at various stages of pattern development. Support for the model could also come from the discovery of certain kinds of hereditary limb defects.     

Enterobacteriaceae and Pseudomonas aeruginosa Recovered from Vegetable Salads

Klebsiella, Enterobacter, and Serratia were recovered frequently in high counts from vegetable salads. Pseudomonas aeruginosa, although isolated frequently, was in lower counts.     

Risk-Cost Trade Off Considerations for Contaminated Sediment Disposal

Delays in dredging and inability to dredge the nation's harbors, due to the presence of contaminated sediments and the lack of environmentally acceptable disposal sites are interfering with shipping activities and hampering trade growth. The United States Government is committed to provide continuing support to the port industry's goals for enhancing economic growth while protecting, conserving and restoring natural resources within coastal aquatic lands. The government's commitment has resulted in the articulation of a national dredging policy in the Action Plan for Improvement of the Dredging Process in the United States. This national challenge calls for a systematic and consistent decision making approach to dredging and disposal including contaminated sediment management. In building an effective decision mak ing framework for costs, risk reduction and potential beneficial uses of the disposal material must be considered in identifying and evaluating environmentally acceptable and cost-effective disposal alternatives. A conceptual framework for applying a risk-cost trade off approach in making decisions regarding contaminated sediment disposal is presented and applied to a hypothetical disposal scenario involving three alternatives: deepwater confined disposal, nearshore fill or capping and, upland disposal. The approach entails the performance of sequential evaluations consisting of risk analysis, estimation of costs, integration of the results into a computational framework for trade-off analysis, and the application of decision analytical tools to build consensus among stakeholders and the general public in selecting a preferred alternative.     

B Cell Responses to HIV Antigen Are a Potent Correlate of Viremia in HIV-1 Infection and Improve with PD-1 Blockade

Infection with Human Immunodeficiency Virus Type 1 (HIV-1) induces defects of both cellular and humoral immune responses. Impaired CD4+ T cell help and B cell dysfunction may partially explain the low frequency of broadly neutralizing antibodies in HIV-infected individuals. To understand the extent of B cell dysfunction during HIV infection, we assessed the level of B cell activation at baseline and after stimulation with a variety of antigens. Increased levels of viremia were associated with higher baseline expression of the activation marker CD86 on B cells and with decreased ability of B cells to increase expression of CD86 after in vitro stimulation with inactivated HIV-1. In a series of cell isolation experiments B cell responses to antigen were enhanced in the presence of autologous CD4+ T cells. HIV infected individuals had a higher frequency of PD-1 expression on B cells compared to HIV- subjects and PD-1 blockade improved B cell responsiveness to HIV antigen, suggesting that inhibitory molecule expression during HIV-1 infection may contribute to some of the observed B cell defects. Our findings demonstrate that during chronic HIV infection, B cells are activated and lose full capacity to respond to antigen, but suppression of inhibitory pressures as well as a robust CD4+ T cell response may help preserve B cell function.     

Susceptibility of Cypriot Tuta absoluta populations to four targeted insecticides and control failure likelihood

Tuta absoluta, known as the South American tomato pinworm, is one of the most disastrous pests of tomato cultivations, presently menacing tomato cultivations worldwide. In 2006, T. absoluta invaded Spain from South America. Since then, it was rapidly spread to most European, African and Asian countries. Such alien invasive species can minimize crop production, whereas the increasing use of insecticides raises various environmental concerns as well as on control costs, control failure and the toxicity to non‐target organisms. The S. American tomato pinworm is mostly controlled by chemical insecticides, and failure to control it is not a rare phenomenon. Resistance to numerous insecticides has been reported and is mainly due to the fact that farmers do not follow a sustainable resistance management scheme. Several examples have been reported from several countries where the tomato pinworm is present. In order to develop a successful insecticide resistance management (IRM) strategy for any major pest, one needs to identify the baseline toxicity to insecticides and then monitor susceptibility levels . In Cyprus, the current status of susceptibility levels to the main insecticides that are used to control T. absoluta has never been studied before. Herein, nine Cypriot populations of the pest were subjected to laboratory bioassays between 2016 and 2018 using the main insecticides applied against it. We found that the insecticides chlorantraniliprole and indoxacarb could not control the Cypriot T. absoluta populations anymore, with a resistance ratio (RR) >28 and 3–23, respectively. Furthermore, mortality achieved by those two insecticides was 20.6%–72% for chlorantraniliprole and 27.5%–78% for indoxacarb. However, the insecticides emamectin benzoate and spinosad are very effective, since mortality to both of them ranged between 99.5% and 100%.     

Regulation of Ang2 release by PTEN/PI3‐kinase/Akt in lung microvascular endothelial cells

Angiopoietin‐2 (Ang2) is a Tie‐2 ligand that destabilizes vascular structures, allowing for neovascularization or vessel regression depending on local vascular endothelial cell growth factor (VEGF) concentrations. Although various stimuli have been shown to affect Ang2 expression, information on the underlying mechanisms involved in Ang2 production in endothelial cells (EC) is just beginning to emerge. In the present study, we have used adenovirus‐mediated gene transfer and pharmacological inhibitors to examine the role of the PTEN/PI3‐K/Akt pathway on Ang2 release. Inhibition of PI3‐kinase with wortmannin led to a stimulation of basal Ang2 release in EC, while overexpression of an active form of Akt reduced Ang2. In addition, adenovirus‐mediated gene transfer of the phosphatase PTEN stimulated Ang2 release. Incubation of the cells with Ang1, an agent that activates the PI3‐K/Akt pathway in EC, reduced Ang2 release. This effect of Ang1 could be prevented by wortmannin and LY‐294002 pretreatment. Similarly, in VEGF‐treated EC the increase in Ang2 production observed was greater in the presence of a PI3‐K inhibitor. Our observations that PTEN acts as a positive modulator of Ang2 release, while activation of the PI3‐K/Akt pathway downregulates Ang2, reveal an additional mechanism through which the PTEN/PI3‐K/Akt pathway could affect the angiogenic process. J. Cell. Physiol. 209: 239, 2006. © 2006 Wiley‐Liss, Inc.     

CD8+ T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis

Objective

To study the prevalence of respiratory and atopic symptoms in (young) adults born prematurely, differences between those who did and did not develop Bronchopulmonary Disease (BPD) at neonatal age and differences in respiratory health between males and females.

Methods

Design: Prospective cohort study. Setting: Nation wide follow-up study, the Netherlands. Participants: 690 adults (19 year old) born with a gestational age below 32 completed weeks and/or with a birth weight less than 1500 g. Controls were Dutch participants of the European Community Respiratory Health Survey (ECRHS). Main outcome measures: Presence of wheeze, shortness of breath, asthma, hay fever and eczema using the ECRHS-questionnaire

Results

The prevalence of doctor-diagnosed asthma was significantly higher in the ex-preterms than in the general population, whereas eczema and hay fever were significant lower. Women reported more symptoms than men. Preterm women vs controls: asthma 13% vs 5% (p < 0.001); hay fever 8% vs 20% (p < 0.001); eczema 10% vs 42% (p < 0.001). Preterm men vs controls: asthma 9% vs 4% (p = 0.007); hay fever 8% vs 17% (p = 0.005); eczema 9% vs 31% (p < 0.001) Preterm women reported more wheeze and shortness of breath during exercise (sob) than controls: wheeze 30% vs 22% (p = 0.009); sob 27% vs 16% (p < 0.001); 19-year-old women with BPD reported a higher prevalence of doctor diagnosed asthma compared to controls (24% vs 5% p < 0.001) and shortness of breath during exercise (43% vs 16% p = 0.008). The prevalence of reported symptoms by men with BPD were comparable with the controls.

Conclusion

Our large follow-up study shows a higher prevalence of asthma, wheeze and shortness of breath in the prematurely born young adults. 19-year-old women reported more respiratory symptoms than men. Compared to the general population atopic diseases as hay fever and eczema were reported less often.     

Inhibin secretion in women with the polycystic ovary syndrome before and after treatment with progesterone

Objectives  

It has been suggested that inhibin secretion is altered in women with the polycystic ovary syndrome (PCOS). However, the contribution of a preceding luteal phase has not been taken into account. The aim of the present study was to investigate whether progesterone in the context of a simulated luteal phase affects basal and FSH-induced inhibin secretion in women with PCOS and elevated LH.