Unfolding of the chromatin fiber driven by overexpression of noninteracting bridging factors

Nuclear molecules control the functional properties of the chromatin fiber by shaping its morphological properties. The biophysical mechanisms controlling how bridging molecules compactify chromatin are a matter of debate. On the one side, bridging molecules could cross-link faraway sites and fold the fiber through the formation of loops. Interacting bridging molecules could also mediate long-range attractions by first tagging different locations of the fiber and then undergoing microphase separation. Using a coarse-grained model and Monte Carlo simulations, we study the conditions leading to compact configurations both for interacting and noninteracting bridging molecules. In the second case, we report on an unfolding transition at high densities of the bridging molecules. We clarify how this transition, which disappears for interacting bridging molecules, is universal and controlled by entropic terms. In general, chains are more compact in the case of interacting bridging molecules because interactions are not valence limited. However, this result is conditional on the ability of our simulation methodology to relax the system toward its ground state. In particular, we clarify how, unless using reaction dynamics that change the length of a loop in a single step, the system is prone to remain trapped in metastable, compact configurations featuring long loops.     

TFG binds LC3C to regulate ULK1 localization and autophagosome formation

The early secretory pathway and autophagy are two essential and evolutionarily conserved endomembrane processes that are finely interlinked. Although growing evidence suggests that intracellular trafficking is important for autophagosome biogenesis, the molecular regulatory network involved is still not fully defined. In this study, we demonstrate a crucial effect of the COPII vesicle‐related protein TFG (Trk‐fused gene) on ULK1 puncta number and localization during autophagy induction. This, in turn, affects formation of the isolation membrane, as well as the correct dynamics of association between LC3B and early ATG proteins, leading to the proper formation of both omegasomes and autophagosomes. Consistently, fibroblasts derived from a hereditary spastic paraparesis (HSP) patient carrying mutated TFG (R106C) show defects in both autophagy and ULK1 puncta accumulation. In addition, we demonstrate that TFG activity in autophagy depends on its interaction with the ATG8 protein LC3C through a canonical LIR motif, thereby favouring LC3C‐ULK1 binding. Altogether, our results uncover a link between TFG and autophagy and identify TFG as a molecular scaffold linking the early secretion pathway to autophagy.     

Unveiling the social performance of selected agri-food chains in Costa Rica: the case of green coffee,raw milk and leafy vegetables

The International Journal of Life Cycle Assessment - Several frameworks coincide in the importance of addressing social impacts to ensure sustainability. However, the agri-food sector, regarded as...     

Early and Late De Novo Tumors after Liver Transplantation in Adults: The Late Onset of Bladder Tumors in Men

Background

De novo tumors (DNT) after liver transplantation (LT) represent a growing concern.

Patients and Methods

We analyzed the incidence of DNT, type, time of onset, risk factors and mortality (as of 2010) in 494 adult patients transplanted in the last 26 years (1983–2009).

Results

DNT occurred in 41 (8.3%) of the patients. The Standardized Incidence Ratio (SIR) compared with the Italian population was 1.8. There was a higher incidence in males (SIR 2.0), an expected extremely high rate of Kaposi’s sarcoma (SIR 127.95) and unexpected higher rates of tumors of the bladder in males (SIR 3.3). The incidence of DNT was higher within the first two years of LT (SIR 2.7) for Kaposi’s sarcoma (SIR 393.3) and after 10 years (SIR 1.7) for bladder tumors (SIR 10.6). Multivariate analysis identified alcoholic cirrhosis (HR = 3.0, 95% CI = 1.2–7.8) and sclerosing cholangitis (HR = 3.5, 95% CI = 1.1–11.3) in the recipient as main risk factors for the occurrence of DNT.

Conclusions

Surveillance protocols for DNT must be specifically oriented to patients transplanted for alcoholic cirrhosis and sclerosing cholangitis. They should focus on early detection of Kaposi’s sarcomas, and more remarkably, on late development bladder tumors in men after LT.     

Molecular validation of Sarcodon quercinofibulatus, a species of the S. imbricatus complex associated with Fagaceae, and notes on Sarcodon

Morphological and molecular phylogenetic analyses revealed that Italian and Mexican collections of an unknown Sarcodon species of the S. imbricatus complex associated with Fagaceae (Castanea and Quercus), were assignable to Sarcodon quercinofibulatus, a species recently described from Spain. The species, characterized by a light brown-hazelnut coloured pileus surface eventually breaking into large and coarse scales, was recognized as independent from Sarcodon imbricatus and S. squamosus. S. aspratus, usually synonymized with S. imbricatus, is a different species. S. squamosus collections from montane and Mediterranean pine woodlands were shown to be conspecific. Four sections of Sarcodon (Sarcodon, Violacei, Squamiceps and Scabrosi) established by Maas Geesteranus (Verh K ned Akad Wet III, 65: 1–127, 1975) only on morphological basis, are here confirmed as monophyletic.     

Generation and application of signaling pathway reporter lines in zebrafish

In the last years, we have seen the emergence of different tools that have changed the face of biology from a simple modeling level to a more systematic science. The transparent zebrafish embryo is one of the living models in which, after germline transformation with reporter protein-coding genes, specific fluorescent cell populations can be followed at single-cell resolution. The genetically modified embryos, larvae and adults, resulting from the transformation, are individuals in which time lapse analysis, digital imaging quantification, FACS sorting and next-generation sequencing can be performed in specific times and tissues. These multifaceted genetic and cellular approaches have permitted to dissect molecular interactions at the subcellular, intercellular, tissue and whole-animal level, thus allowing integration of cellular and developmental genetics with molecular imaging in the resulting frame of modern biology. In this review, we describe a new step in the zebrafish road to system biology, based on the use of transgenic biosensor animals expressing fluorescent proteins under the control of signaling pathway-responsive cis-elements. In particular, we provide here the rationale and details of this powerful tool, trying to focus on its huge potentialities in basic and applied research, while also discussing limits and potential technological evolutions of this approach.     

Visual Working Memory Contents Bias Ambiguous Structure from Motion Perception

The way we perceive the visual world depends crucially on the state of the observer. In the present study we show that what we are holding in working memory (WM) can bias the way we perceive ambiguous structure from motion stimuli. Holding in memory the percept of an unambiguously rotating sphere influenced the perceived direction of motion of an ambiguously rotating sphere presented shortly thereafter. In particular, we found a systematic difference between congruent dominance periods where the perceived direction of the ambiguous stimulus corresponded to the direction of the unambiguous one and incongruent dominance periods. Congruent dominance periods were more frequent when participants memorized the speed of the unambiguous sphere for delayed discrimination than when they performed an immediate judgment on a change in its speed. The analysis of dominance time-course showed that a sustained tendency to perceive the same direction of motion as the prior stimulus emerged only in the WM condition, whereas in the attention condition perceptual dominance dropped to chance levels at the end of the trial. The results are explained in terms of a direct involvement of early visual areas in the active representation of visual motion in WM.     

Curcuma longa L. as a Therapeutic Agent in Intestinal Motility Disorders. 2: Safety Profile in Mouse

Background

Curcuma extract exerts a myorelaxant effect on the mouse intestine. In view of a possible use of curcuma extract in motor functional disorders of the gastrointestinal tract, a safety profile study has been carried out in the mouse.

Methods

Thirty mice were used to study the in vitro effect of curcuma on gallbladder, bladder, aorta and trachea smooth muscular layers and hearth inotropic and chronotropic activity. The myorelaxant effect on the intestine was also thoroughly investigated. Moreover, curcuma extract (200 mg/Kg/day) was orally administered to twenty mice over 28 days and serum liver and lipids parameters were evaluated. Serum, bile and liver bile acids qualitative and quantitative composition was were also studied.

Results

In the intestine, curcuma extract appeared as a not competitive inhibitor through cholinergic, histaminergic and serotoninergic receptors and showed spasmolytic effect on K⁺ induced contraction at the level of L type calcium channels. No side effect was observed on bladder, aorta, trachea and heart when we used a dose that is effective on the intestine. An increase in gallbladder tone and contraction was observed. Serum liver and lipids parameters were normal, while a slight increase in serum and liver bile acids concentration and a decrease in bile were observed.

Conclusions

Although these data are consistent with the safety of curcuma extract as far as its effect on the smooth muscular layers of different organs and on the heart, the mild cholestatic effect observed in absence of alteration of liver function tests must be further evaluated and the effective dose with minimal side effects considered.