Heregulin β1 induces the down regulation and the ubiquitin-proteasome degradation pathway of p185HER2 oncoprotein

AbstractAnalysis of the fate of the p185HER2 oncoprotein following activation by heregulin β1 revealed the induction of the tyrosine-phosphorylation, down-modulation, and polyubiquitination of p185HER2. Receptor ubiquitination was suppressed in cells treated with heregulin β1 in the presence of sodium azide, an inhibitor of ATP-dependent reactions, or genistein, a tyrosine kinase protein inhibitor, indicating the requirement for kinase activity and ATP in p185HER2 polyubiquitination. Ubiquitinated p185HER2 was degradated by the 26S proteasome proteolytic pathway. Kinetics and inhibition experiments indicated that endocytosis of the receptor occurs downstream of the initiation of the degradation process

Quantum Circuits for the Unitary Permutation Problem

We consider the Unitary Permutation problem which consists, given $n$ unitary gates $U_1, \ldots, U_n$ and a permutation $\sigma$ of $\{1,\ldots, n\}$, in applying the unitary gates in the order specified by $\sigma$, i.e. in performing $U_{\sigma(n)}\ldots U_{\sigma(1)}$. This problem has been introduced and investigated by Colnaghi et al. where two models of computations are considered. This first is the (standard) model of query complexity: the complexity measure is the number of calls to any of the unitary gates $U_i$ in a quantum circuit which solves the problem. The second model provides quantum switches and treats unitary transformations as inputs of second order. In that case the complexity measure is the number of quantum switches. In their paper, Colnaghi et al. have shown that the problem can be solved within $n^2$ calls in the query model and $\frac{n(n-1)}2$ quantum switches in the new model. We refine these results by proving that $n\log_2(n) +\Theta(n)$ quantum switches are necessary and sufficient to solve this problem, whereas $n^2-2n+4$ calls are sufficient to solve this problem in the standard quantum circuit model. We prove, with an additional assumption on the family of gates used in the circuits, that $n^2-o(n^{7/4+\epsilon})$ queries are required, for any $\epsilon >0$. The upper and lower bounds for the standard quantum circuit model are established by pointing out connections with the permutation as substring problem introduced by Karp.Comment: 8 pages, 5 figure

[Assessment of pulmonary function in a follow-up of premature infants: our experience].

Respiratory diseases are a major cause of morbidity in neonates, especially preterm infants; a long term complication of prematurity such as bronchopulmonary dysplasia (BPD) is particularly relevant today. The exact role of the Pulmonary Function Test (PFT) in this area is not yet well defined; the PFT in newborns and infants - in contrast to what happens in uncooperative children and adults - are routinely used only in a few centers. The assessment of pulmonary function in newborns and infants, however, is nowadays possible with the same reliability that in cooperative patients with the possibility to extend the assessment of polmonary function from bench to bed. The assessment of pulmonary function must be carried out with non invasive and safe methods, at the bedside, with the possibility of continuous monitoring and providing adequate calculation and management of data. The ability to assess lung function helps to define the mechanisms of respiratory failure, improving the treatment and its effects and is therefore a useful tool in the follow-up of newborn and infant with pulmonary disease

The 67-kDa laminin receptor originated from a ribosomal protein that acquired a dual function during evolution.

The 67-kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that mediates high-affinity interactions between cells and laminin. Overexpression of this protein in tumor cells has been related to tumor invasion and metastasis. Thus far, only a full-length gene encoding a 37-kDa precursor protein (37LRP) has been isolated. The finding that the cDNA for the 37LRP is virtually identical to a cDNA encoding the ribosomal protein p40 has suggested that 37LRP is actually a component of the translational machinery, with no laminin-binding activity. On the other hand, a peptide of 20 amino acids deduced from the sequence of 37LR/p40 was shown to exhibit high laminin-binding activity. The evolutionary relationship between 23 sequences of 37LRP/p40 proteins was analyzed. This phylogenetic analysis indicated that all of the protein sequences derive from orthologous genes and that the 37LRP is indeed a ribosomal protein that acquired the novel function of laminin receptor during evolution. The evolutionary analysis of the sequence identified as the laminin-binding site in the human protein suggested that the acquisition of the laminin-binding capability is linked to the palindromic sequence LMWWML, which appeared during evolution concomitantly with laminin

The three-dimensional structure of Galactic molecular cloud complexes out to 2.5 kpc

Knowledge of the three-dimensional structure of Galactic molecular clouds is important for understanding how clouds are affected by processes such as turbulence and magnetic fields and how this structure effects star formation within them. Great progress has been made in this field with the arrival of the Gaia mission, which provides accurate distances to $\sim10^{9}$ stars. Combining these distances with extinctions inferred from optical-IR, we recover the three-dimensional structure of 16 Galactic molecular cloud complexes at $\sim1$pc resolution using our novel three-dimensional dust mapping algorithm \texttt{Dustribution}. Using \texttt{astrodendro} we derive a catalogue of physical parameters for each complex. We recover structures with aspect ratios between 1 and 11, i.e.\ everything from near-spherical to very elongated shapes. We find a large variation in cloud environments that is not apparent when studying them in two-dimensions. For example, the nearby California and Orion A clouds look similar on-sky, but we find California to be more sheet-like, and massive, which could explain their different star-formation rates. In Carina, our most distant complex, we observe evidence for dust sputtering, which explains its measured low dust mass. By calculating the total mass of these individual clouds, we demonstrate that it is necessary to define cloud boundaries in three-dimensions in order to obtain an accurate mass; simply integrating the extinction overestimates masses. We find that Larson's relationship on mass vs radius holds true whether you assume a spherical shape for the cloud or take their true extents.Comment: accepted for publication by MNRAS, 23 pages, 9 figures, 3 table

Micro- and Nanoplastics’ Effects on Protein Folding and Amyloidosis

A significant portion of the world's plastic is not properly disposed of and, through various processes, is degraded into microscopic particles termed micro- and nanoplastics. Marine and terrestrial faunae, including humans, inevitably get in contact and may inhale and ingest these microscopic plastics which can deposit throughout the body, potentially altering cellular and molecular functions in the nervous and other systems. For instance, at the cellular level, studies in animal models have shown that plastic particles can cross the blood-brain barrier and interact with neurons, and thus affect cognition. At the molecular level, plastics may specifically influence the folding of proteins, induce the formation of aberrant amyloid proteins, and therefore potentially trigger the development of systemic and local amyloidosis. In this review, we discuss the general issue of plastic micro- and nanoparticle generation, with a focus on their effects on protein folding, misfolding, and their possible clinical implications

Mechanisms of goethite dissolution in the presence of desferrioxamine B and Suwannee River fulvic acid at pH 6.5

Siderophores are Fe3+ specific low MW chelating ligands secreted by microorganisms in response to Fe stress. Low MW organic acids such as oxalate have been shown to enhance siderophore mediated dissolution of Fe3+ oxides. However, the effect of fulvic acid presence on siderophore function remains unknown. We used batch dissolution experiments to investigate Fe release from goethite in the goethite-fulvic acid desferrioxamine B (goethite-SRFA-DFOB) ternary system. Experiments were conducted at pH 6.5 while varying reagent addition sequence. FTIR and UV-Vis spectroscopy were employed to characterise the Fe-DFOB, Fe-SRFA and DFOB–SRFA complexes. Iron released from goethite in the presence of SRFA alone was below detection limit. In the presence of both SRFA and DFOB, dissolved Fe increased with reaction time, presence of the DFOB-SRFA complex, and where SRFA was introduced prior to DFOB. FTIR data show that in the ternary system, Fe3+ is complexed primarily to oxygen of the DFOB hydroxamate group, whilst the carboxylate C=O of SRFA forms an electrostatic association with the terminal NH3+ of DFOB. We propose that SRFA sorbed to goethite lowers the net positive charge of the oxide surface, thus facilitating adsorption of cationic DFOB and subsequent Fe3+ chelation and release. Furthermore, the sorbed SRFA weakens Fe-O bonds at the goethite surface, increasing the population of kinetically labile Fe. This work demonstrates the positive, though indirect role of SRFA in increasing the bioavailability of Fe3+