cry1 and GPA1 signaling genetically interact in hook opening and anthocyanin synthesis in Arabidopsis

While studying blue light-independent effects of cryptochrome 1 (cry1) photoreceptor, we observed premature opening of the hook in cry1 mutants grown in complete darkness, a phenotype that resembles the one described for the heterotrimeric G-protein α subunit (GPA1) null mutant gpa1. Both cry1 and gpa1 also showed reduced accumulation of anthocyanin under blue light. These convergent gpa1 and cry1 phenotypes required the presence of sucrose in the growth media and were not additive in the cry1 gpa1 double mutant, suggesting context-dependent signaling convergence between cry1 and GPA1 signaling pathways. Both, gpa1 and cry1 mutants showed reduced GTP-binding activity. The cry1 mutant showed wild-type levels of GPA1 mRNA or GPA1 protein. However, an anti-transducin antibody (AS/7) typically used for plant Gα proteins, recognized a 54?kDa band in the wild type but not in gpa1 and cry1 mutants. We propose a model where cry1-mediated post-translational modification of GPA1 alters its GTP-binding activity.     

Improving inhaler adherence in patients with Chronic Obstructive Pulmonary Disease: a cost-effectiveness analysis

Background

The PHARMACOP-intervention significantly improved medication adherence and inhalation technique for patients with COPD compared with usual care. This study aimed to evaluate its cost-effectiveness.

Methods

An economic analysis was performed from the Belgian healthcare payer’s perspective. A Markov model was constructed in which a representative group of patients with COPD (mean age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume in 1 second of % predicted of 50), was followed for either receiving the 3-month PHARMACOP-intervention or usual care. Three types of costs were calculated: intervention costs, medication costs and exacerbation costs. Outcome measures included the number of hospital-treated exacerbations, cost per prevented hospital-treated exacerbation and cost per Quality Adjusted Life-Year. Follow-up was 1 year in the basecase analysis. Sensitivity and scenario analyses (including long-term follow-up) were performed to assess uncertainty.

Results

In the basecase analysis, the average overall costs per patient for the PHARMACOP-intervention and usual care were €2,221 and €2,448, respectively within the 1-year time horizon. This reflects cost savings of €227 for the PHARMACOP-intervention. The PHARMACOP-intervention resulted in the prevention of 0.07 hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for usual care). Results showed robust cost-savings in various sensitivity analyses.

Conclusions

Optimization of current pharmacotherapy (e.g. close monitoring of inhalation technique and medication adherence) has been shown to be cost-saving and should be considered before adding new therapies.     

Biologically relevant effects of mRNA amplification on gene expression profiles

Background  

Gene expression microarray technology permits the analysis of global gene expression profiles. The amount of sample needed limits the use of small excision biopsies and/or needle biopsies from human or animal tissues. Linear amplification techniques have been developed to increase the amount of sample derived cDNA. These amplified samples can be hybridised on microarrays. However, little information is available whether microarrays based on amplified and unamplified material yield comparable results.     

Chromosome phylogeny of the subfamily Pitheciinae (Platyrrhini,Primates) by classic cytogenetics and chromosome painting

Background  

The New World monkey (Platyrrhini) subfamily Pitheciinae is represented by the genera Pithecia, Chiropotes and Cacajao. In this work we studied the karyotypes of Pithecia irrorata (2n = 48) and Cacajao calvus rubicundus (2n = 45 in males and 2n = 46 in females) by G- and C-banding, NOR staining and chromosome painting using human and Saguinus oedipus whole chromosome probes. The karyotypes of both species were compared with each other and with Chiropotes utahicki (2n = 54) from the literature.     

STIL,a peculiar molecule from styles,specifically dephosphorylates the pollen receptor kinase LePRK2 and stimulates pollen tube growth <Emphasis Type="Italic">in vitro</Emphasis>

Background  

LePRK1 and LePRK2 are two pollen receptor kinases localized to the plasma membrane, where they are present in a high molecular weight complex (LePRK complex). LePRK2 is phosphorylated in mature and germinated pollen, but is dephosphorylated when pollen membranes are incubated with tomato or tobacco style extracts.     

Direct anti-metastatic efficacy by the DNA enzyme Dz13 and downregulated MMP-2, MMP-9 and MT1-MMP in tumours

The DNA enzyme Dz13, targeted against the oncogene c-Jun, is capable of inhibiting various model tumours in mice albeit in ectopic models of neoplasia. In previous studies using orthotopic models of disease, the inhibitory effects of Dz13 on secondary growth was a direct result of growth inhibition at the primary lesion site. Thus, the direct and genuine effects on metastasis were not gauged. In this study, Dz13 was able to inhibit both locoregional and distal metastasis of tumour cells in mice, in studies where the primary tumours were unaffected due to the late and clinically-mimicking nature of treatment commencement. In addition, the effect of Dz13 against tumours has now been extended to encompass breast and prostate cancer. Dz13 upregulated the matrix metalloproteinase (MMP)-2 and MMP-9, and decreased expression of MT1-MMP (MMP-14) in cultured tumour cells. However, in sections of ectopic tumours treated with Dz13, both MMP-2 and MMP-9 were downregulated. Thus, not only is Dz13 able to inhibit tumour growth at the primary site, but also able to decrease the ability of neoplastic cells to metastasise. These findings further highlight the growing potential of Dz13 as an antineoplastic agent.     

TIP5;1 is an aquaporin specifically targeted to pollen mitochondria and is probably involved in nitrogen remobilization in Arabidopsis thaliana

In plant sexual reproduction, water and solute movement are tightly regulated, suggesting the involvement of aquaporins. We previously identified TIP5;1 and TIP1;3 as the only Arabidopsis aquaporin genes that are selectively and highly expressed in mature pollen, and showed that they can transport both water and urea when expressed in Xenopus oocytes. Here, we show that TIP5;1 has unusual characteristics, as its water transport activity is regulated by pH. Analysis of the water transport activity of a mutant version of TIP5;1 (TIP5;1-H131A) and amino acid alignment with other plant aquaporins regulated by pH suggested that a conserved motif is involved in pH sensing. GFP-TIP5;1 is located in the mitochondria of pollen tubes. The single mutants tip1;3 and tip5;1, as well as the tip1;3 tip5;1 double mutant, are fertile, but all mutants had shorter than normal pollen tubes when germinated in vitro in the absence of exogenous nitrogen. Thus, we propose that TIP5;1 and TIP1;3 are involved in nitrogen recycling in pollen tubes of Arabidopsis thaliana.     

Reproductive phenology of the Mediterranean seagrasses Posidonia oceanica (L.) Delile, Cymodocea nodosa (Ucria) Aschers., and Zostera noltii Hornem.

Investigations on the sexual reproduction of Posidonia oceanica (L.) Delile, Cymodocea nodosa (Ucria) Aschers. and Zostera noltii Hornem. were conducted in situ from 1979 to 1988 in beds around the island of Ischia. Seed germination and phenological features of seedlings of P. oceanica and C. nodosa were observed in situ and in the laboratory. The reproductive cycles showed, for each species, different timing of start and duration of flowering, fruiting and germination. Posidonia oceanica flowers always appeared in September in shallow stands and in November in stands deeper than 15 m. This time delay seems to be related to the different maximum summer temperatures found at those depths. This species did not show dormancy. Cymodocea nodosa flowering was always recorded after the minimum winter temperature (April–May); germination of the seeds followed after 8–10 months of dormancy. Zostera noltii flowers were always recorded in July, with fruiting in August. The life cycles of these species seem to be related to the annual temperature range rather than to other environmental parameters. The different reproductive strategies adopted by each species are discussed.     

YAP‐TEAD signaling promotes basal cell carcinoma development via a c‐JUN/AP1 axis

The mammalian Hippo signaling pathway, through its effectors YAP and TAZ, coerces epithelial progenitor cell expansion for appropriate tissue development or regeneration upon damage. Its ability to drive rapid tissue growth explains why many oncogenic events frequently exploit this pathway to promote cancer phenotypes. Indeed, several tumor types including basal cell carcinoma (BCC) show genetic aberrations in the Hippo (or YAP/TAZ) regulators. Here, we uncover that while YAP is dispensable for homeostatic epidermal regeneration, it is required for BCC development. Our clonal analyses further demonstrate that the few emerging Yap‐null dysplasia have lower fitness and thus are diminished as they progress to invasive BCC. Mechanistically, YAP depletion in BCC tumors leads to effective impairment of the JNK‐JUN signaling, a well‐established tumor‐driving cascade. Importantly, in this context, YAP does not influence canonical Wnt or Hedgehog signaling. Overall, we reveal Hippo signaling as an independent promoter of BCC pathogenesis and thereby a viable target for drug‐resistant BCC.     

Evidence for a role of the cytoskeleton in the in vitro folliculogenesis of the thyroid gland of the fetal rat

Summary Thyrotropic hormone (TSH) or cAMP accelerate the formation of follicular cavities in the explanted thyroid gland of the 15-day-old rat fetus. Cytochalasin B or vinblastine and nocodazole or colchicine, which disorganize microfilamental and microtubular structures respectively, inhibit or completely block in vitro-induced folliculogenesis. Exposure of the thyroid tissue to lumicolchicine, a structural isomer of colchicine deprived of antimicrotubular activity, does not inhibit the activation of folliculogenesis induced by TSH. These results are strong evidence for the supposition that microfilaments and microtubules are involved in the TSH-stimulated mechanisms resulting in thyroid folliculogenesis. Folliculogenesis requires the integrity of both microfilaments and microtubules.