Balancing signals in the intestinal niche

During intestinal regeneration, opposing gradients of Wnt and BMP signaling ensure successful differentiation along the crypt/villus axis. In this issue of The EMBO Journal, Horiguchi et al ( 2017 ) show how intestinal subepithelial myofibroblasts can influence cell fate decisions in the regenerating intestine via autocrine secretion of angiopoietin‐like protein 2 (ANGPTL2).     

Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene

1. Download high-res image (255KB)
2. Download full-size image

     

Association patterns of bottlenose dolphins (Tursiops truncatus) in Bahía San Antonio,Argentina

This study aims to investigate the association patterns of a small and resident population of bottlenose dolphins (Tursiops truncatus) in Bahía San Antonio (Argentina), and assess any seasonal variation in view of the reported seasonal variation in the population's grouping behavior. The estimation of social differentiation (S) was 0.29 (SE = 0.08), suggesting a homogenous society. The half‐weight index (HWI) averaged 0.23 (± 0.06), with evidence of long‐term preferred associations. However, data showed seasonal variation in the association patterns. In winter, when large groups were reported in this population, HWI values averaged 0.30 (± 0.09) with no indication of preferred or avoided associations. However, during summer, when group size was generally small, HWI values averaged 0.14 (± 0.07), with an indication of preferred/avoided associations. This study indicates that the social structure of the bottlenose dolphins in Bahía San Antonio seems relatively homogenous and flexible over time, with the formation of a random social network at times when large aggregations are formed, and a more disconnected network made up of strongly connected components when the cost of grouping is high.     

Protein Kinase C Activation Upregulates Intercellular Adhesion of α-Catenin–negative Human Colon Cancer Cell Variants via Induction of Desmosomes

The α-catenin molecule links E-cadherin/ β-catenin or E-cadherin/plakoglobin complexes to the actin cytoskeleton. We studied several invasive human colon carcinoma cell lines lacking α-catenin. They showed a solitary and rounded morphotype that correlated with increased invasiveness. These round cell variants acquired a more normal epithelial phenotype upon transfection with an α-catenin expression plasmid, but also upon treatment with the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Video registrations showed that the cells started to establish elaborated intercellular junctions within 30 min after addition of TPA. Interestingly, this normalizing TPA effect was not associated with α-catenin induction. Classical and confocal immunofluorescence showed only minor TPA-induced changes in E-cadherin staining. In contrast, desmosomal and tight junctional proteins were dramatically rearranged, with a conversion from cytoplasmic clusters to obvious concentration at cell–cell contacts and exposition at the exterior cell surface. Electron microscopical observations revealed the TPA-induced appearance of typical desmosomal plaques. TPA-restored cell–cell adhesion was E-cadherin dependent as demonstrated by a blocking antibody in a cell aggregation assay. Addition of an antibody against the extracellular part of desmoglein-2 blocked the TPA effect, too. Remarkably, the combination of anti–E-cadherin and anti-desmoglein antibodies synergistically inhibited the TPA effect.

Our studies show that it is possible to bypass the need for normal α-catenin expression to establish tight intercellular adhesion by epithelial cells. Apparently, the underlying mechanism comprises upregulation of desmosomes and tight junctions by activation of the PKC signaling pathway, whereas E-cadherin remains essential for basic cell–cell adhesion, even in the absence of α-catenin.

     

Characterization of proinflammatory cytokine production and CD14 expression by murine alveolar macrophage cell lines

Summary Alveolar macrophages, which play a central role in lung defense, produce cytokines that help orchestrate local inflammatory responses. In sepsis and other pathological conditions, bacterial lipopolysaccharide endotoxin can induce alveolar macrophages (AM) to release proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1, and interleukin-6. Studying the mechanisms that control alveolar macrophage cytokine production may lead to better therapies for conditions involving inflammatory lung injury. We and others have noted significant differences between alveolar macrophages and peritoneal macrophages, but large numbers of human or murine alveolar macrophages are rarely available for detailed mechanistic studies. We have obtained three murine alveolar macrophage cell lines (AMJ2C8, AMJ2C11, and AMJ2C20) and have begun to characterize their cytokine responses to proinflammatory stimuli. We measured the effects of endotoxin, interferon gamma, and the combination of the two on production of tumor necrosis factor, interleukin-1 beta, and interleukin-6 in each line. We also studied the expression of the endotoxin receptor CD14 by these cells, and investigated the effect of serum on their endotoxin responsiveness. We show here that all three of the cell lines responded in a manner comparable to that of primary murine alveolar macrophages. Observed variations between these lines may reflect the documented heterogeneity seen in populations of primary alveolar macrophages. These cell lines should expand the repertoire of tools available to investigators studying regulation of murine alveolar macrophage responses.     

Simultaneous determination of eight lipid peroxidation degradation products in urine of rats treated with carbon tetrachloride using gas chromatography with electron-capture detection

One of the major processes that occur as a result of radical-induced oxidative stress is lipid peroxidation (LPO). Degradation of lipid peroxides results in various products, including a variety of carbonyl compounds. In the present study eight different lipid degradation products, i.e., formaldehyde, acetaldehyde, acetone, propanal, butanal, pentanal, hexanal and malondialdehyde were identified and measured simultaneously and quantitatively in rat urine after derivatization with O-(2,3,4,5,6-pentafluorbenzyl)hydroxylamine hydrochloride, extraction with heptane and using gas chromatography–electron-capture detection (GC–ECD). The identity of the respective oximes in urine was confirmed by gas chromatography–negative ion chemical ionization mass spectrometry (GC–NCI-MS). Simultaneously measured standard curves were linear for all oxime-products and the detection limits were between 39.0±5.3 (n=9) and 500±23 (n=9) fmol per μl injected sample. Recoveries of all products from urine or water were 73.0±5.2% and higher. In urine of CCl₄-treated rats an increase in all eight lipid degradation products in urine was found 24 h following exposure. ACON showed the most distinct increase, followed by PROPA, BUTA and MDA. It is concluded that the rapid, selective and sensitive analytical method based on GC–ECD presented here is well suited for routine measurement of eight different lipid degradation products. These products appear to be useful as non-invasive biomarkers for in vivo oxidative stress induced in rats by CCl₄.     

Vieillissement et fertilité de l'homme

The decreased androgen levels in the ageing male have an evident effect on libido, sex life and coital frequency, whereas its role in impotence, the frequency of which increases dramatically in old age, is only marginal. Sperm quality as well as its fertilizing capacity decreases only minimally with age: there is some decrease in motility as well as an increase in percentage of spermatozoa with abnormal morphology, but sperm density remains unchanged, notwithstanding decreased spermatogenesis. After age 25, apparent fecundability of the woman decreases; this is attributable, on the one hand to an increase of the intrauterine mortality and, on the other hand to the declining coital frequency. After age of 35, female fecundity decreases more rapidly, due to changes in female physiology (increased frequency of anovulatory cycles, short luteal phase etc), whereas the normal, age dependent, decrease in coital frequency has little impact on the age pattern of fecundability. As far as the influence of the age pattern on the fecundity of the couple is concerned, it is concluded that the age of the female partner, rather than the age of the husband is the predominant factor determining the fecundability of the couple.     

Mapping resistance to powdery mildew in barley reveals a large-effect nonhost resistance QTL

Key message

Resistance factors against non-adapted powdery mildews were mapped in barley. Some QTLs seem effective only to non-adapted mildews, while others also play a role in defense against the adapted form.The durability and effectiveness of nonhost resistance suggests promising practical applications for crop breeding, relying upon elucidation of key aspects of this type of resistance. We investigated which genetic factors determine the nonhost status of barley (Hordeum vulgare L.) to powdery mildews (Blumeria graminis). We set out to verify whether genes involved in nonhost resistance have a wide effectiveness spectrum, and whether nonhost resistance genes confer resistance to the barley adapted powdery mildew. Two barley lines, SusBgt_SC and SusBgt_DC, with some susceptibility to the wheat powdery mildew B. graminis f.sp. tritici (Bgt) were crossed with cv Vada to generate two mapping populations. Each population was assessed for level of infection against four B. graminis ff.spp, and QTL mapping analyses were performed. Our results demonstrate polygenic inheritance for nonhost resistance, with some QTLs effective only to non-adapted mildews, while others play a role against adapted and non-adapted forms. Histology analyses of nonhost interaction show that most penetration attempts are stopped in association with papillae, and also suggest independent layers of defence at haustorium establishment and conidiophore formation. Nonhost resistance of barley to powdery mildew relies mostly on non-hypersensitive mechanisms. A large-effect nonhost resistance QTL mapped to a 1.4 cM interval is suitable for map-based cloning.

     

Photo-identification and satellite telemetry connect southern right whales from South Georgia Island (Islas Georgias del Sur) with multiple feeding and calving grounds in the southwest Atlantic

The sub-Antarctic waters of South Georgia Island (Islas Georgias del Sur, SG/IG) are a regularly visited feeding ground for southern right whales (Eubalaena australis, SRW) in the southwest Atlantic. Satellite telemetry and photo-identification records were compared to better understand the role of SG/IG in the SRW migratory network. We present the first insights from SRW satellite-tracked from the SG/IG feeding ground, habitat use patterns in the Scotia Arc, and movements to Antarctic habitats. Photo-identification comparisons to calving and feeding areas across the South Atlantic and a review of sightings of cetaceans reported from Bird Island (west of SG/IG) since 1979 illuminate long-term habitat use patterns in SG/IG. We present the first recorded migratory movement between SG/IG and multiple countries: Argentina, Uruguay, and Brazil. Photo-identification (1) linked SG/IG to a female SRW with a long-term sighting history in Brazil, and (2) provided the first match between SG/IG and the western Antarctic Peninsula, suggesting the latter could extend the feeding area for southwest Atlantic SRW. Satellite tracking and opportunistic sightings suggest that shelf and coastal waters west of SG/IG represent an important multi-season SRW feeding habitat and add to our overall understanding of habitats and ranges occupied by recovering southwest Atlantic SRW.