Guanosine and GMP increase the number of granular cerebellar neurons in culture: dependence on adenosine A2A and ionotropic glutamate receptors

Purinergic Signalling - The guanine-based purines (GBPs) have essential extracellular functions such as modulation of glutamatergic transmission and trophic effects on neurons and astrocytes. We...     

Multiparametric magnetic resonance imaging-guided salvage radiotherapy in prostate cancer

AimTo analyse the efficacy and toxicity of postprostatectomy SRT in patients with a BCR evaluated with mpMRI.BackgroundMultiparametric magnetic resonance imaging (mpMRI) has the ability to detect the site of pelvic recurrence in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, we do not know the oncological outcomes of mpMRI-guided savage radiotherapy (SRT).ResultsLocal, lymph node, and pelvic bone recurrence was observed in 13, 4 and 2 patients, respectively. PSA levels were significantly lower in patients with negative mpMRI (0.4 ng/mL [0.4]) vs. positive mpMRI (2.2 ng/mL [4.1], p = 0.003). Median planning target volume doses in patients with visible vs. non-visible recurrences were 76 Gy vs. 70 Gy. Overall, mean follow-up was 41 months (6–81). Biochemical relapse-free survival (bRFS) at 3 years was 82.3% and 82.5%, respectively, for the negative and positive mpMRI groups (p = 0.800). Three-year rates of late grade ≥2 urinary and rectal toxicity were 14.8% and 1.9%, respectively; all but one patient recovered without sequelae.ConclusionSRT to the macroscopic recurrence identified by mpMRI is a feasible and well-tolerated option. In this study, there were no differences in bRFS between MRI-positive and MRI-negative patients, indicating effective targeting of MRI-positive lesions.     

Expression and function of the bHLH genes ALCATRAZ and SPATULA in selected Solanaceae species

The genetic mechanisms underlying fruit development have been identified in Arabidopsis and have been comparatively studied in tomato as a representative of fleshy fruits. However, comparative expression and functional analyses on the bHLH genes downstream the genetic network, ALCATRAZ (ALC) and SPATULA (SPT), which are involved in the formation of the dehiscence zone in Arabidopsis, have not been functionally studied in the Solanaceae. Here, we perform detailed expression and functional studies of ALC/SPT homologs in Nicotiana obtusifolia with capsules, and in Capsicum annuum and Solanum lycopersicum with berries. In Solanaceae, ALC and SPT genes are expressed in leaves, and all floral organs, especially in petal margins, stamens and carpels; however, their expression changes during fruit maturation according to the fruit type. Functional analyses show that downregulation of ALC/SPT genes does not have an effect on gynoecium patterning; however, they have acquired opposite roles in petal expansion and have been co‐opted in leaf pigmentation in Solanaceae. In addition, ALC/SPT genes repress lignification in time and space during fruit development in Solanaceae. Altogether, some roles of ALC and SPT genes are different between Brassicaceae and Solanaceae; while the paralogs have undergone some subfunctionalization in the former they are mostly redundant in the latter.     

WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop

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Fitness increases with partner and neighbour allopreening

Altruism and selfishness are fundamental characteristics of human and animal societies. Among colonial biparental species, breeding outcome depends on interactions between mates and neighbours. However, the relationships between cooperation within and among partnerships and fitness have not been fully investigated. We show that in the highly colonial common guillemot (Uria aalge), altruistic behaviour (allopreening) towards a mate was positively related to long-term fitness, whereas allopreening a neighbour was related to current fitness. Turnover is much lower within than between pairs, so our results suggest that allopreening within pairs generates fitness returns at longer timescales than between pairs. Allopreening not only removes ectoparasites and maintains plumage condition, but may also have important social functions. We found a negative relationship between fight rate and allopreen rate between breeding neighbours, with nests exhibiting low breeding success having a higher frequency of fights with neighbours. We also found evidence for reciprocity in allopreening. Thus, allopreening may function as a reciprocal stress reducer, to decrease the likelihood of fights and associated breeding failure. We suggest that altruistic behaviour has long-term benefits for the survival of the offspring when living in a crowded neighbourhood.     

Proteome analysis of chemically induced mouse liver tumors with different genotype

Mouse liver tumors frequently harbor mutations in Ha-ras, B-raf, or Ctnnb1 (encoding beta-catenin). We conducted a proteome analysis with protein extracts from normal mouse liver and from liver tumors which were induced by a single injection of N-nitrosodiethylamine (DEN) as initiator followed by multiple injections of two different polychlorinated biphenyls (PCBs) as tumor promoters, or corn oil as a control. Liver tumors were stratified into two classes: they were either mutated in Ctnnb1 and positive for the marker glutamine synthetase (GS(+)), or they lacked Ctnnb1 mutations and were therefore GS-negative (GS(-)). Proteome analysis by 2-DE and MS revealed 98 significantly deregulated proteins, 44 in GS(+) and 54 in GS(-) tumors. Twelve of these proteins showed expression changes in both tumor types, but only seven of them were deregulated in the same direction. Several of the identified enzymes could be assigned to fundamental metabolic or other cellular pathways with characteristically different alterations in GS(+) and GS(-) tumors such as ammonia and amino acid turnover, cellular energy supply, and calcium homeostasis. Our data suggest that GS(+) and GS(-) tumor cells show a completely different biology and use divergent evolutionary strategies to gain a selective advantage over normal hepatocytes.