Phenolics Composition and Biological Activities Assessment of Leaves,Flowers and Roots Extracts from Erodium glaucophyllum,Erodium hirtum and Erodium guttatum

Biology Bulletin - Erodium glaucophyllum, Erodium hirtum and Erodium guttatum were medicinal herbs from a southern Mediterranean known for its health benefits. There is a strong demand for the find...     

Should I stay or should I go?: Shedding of RPTPs in cancer cells switches signals from stabilizing cell-cell adhesion to driving cell migration

Dissolution of cell-cell adhesive contacts and increased cell-extracellular matrix adhesion are hallmarks of the migratory and invasive phenotype of cancer cells. These changes are facilitated by growth factor binding to receptor protein tyrosine kinases (RTKs). In normal cells, cell-cell adhesion molecules (CAMs), including some receptor protein tyrosine phosphatases (RPTPs), antagonize RTK signaling by promoting adhesion over migration. In cancer, RTK signaling is constitutive due to mutated or amplified RTKs, which leads to growth factor independence or autonomy. An alternative route for a tumor cell to achieve autonomy is to inactivate cell-cell CAMs such as RPTPs. RPTPs directly mediate cell adhesion and regulate both cadherin-dependent adhesion and signaling. In addition, RPTPs antagonize RTK signaling by dephosphorylating molecules activated following ligand binding. Both RPTPs and cadherins are downregulated in tumor cells by cleavage at the cell surface. This results in shedding of the extracellular, adhesive segment and displacement of the intracellular segment, altering its subcellular localization and access to substrates or binding partners. In this commentary we discuss the signals that are altered following RPTP and cadherin cleavage to promote cell migration. Tumor cells both step on the gas (RTKs) and disconnect the brakes (RPTPs and cadherins) during their invasive and metastatic journey.Key words: receptor protein tyrosine kinase, receptor-like protein tyrosine phosphatase, cadherins, cell adhesion, signal transduction, phospholipase C gamma, protein kinase C, catenins, IQGAP1 protein, regulated intramembrane proteolysis     

EFFECTS OF DIETARY SUPPLEMENTAL L-CARNITINE AND ASCORBIC ACID ON PERFORMANCE,CARCASS COMPOSITION AND PLASMA L-CARNITINE CONCENTRATION OF BROILER CHICKS REARED UNDER DIFFERENT TEMPERATURE

The present study was initiated to determine whether dietary supplemental L-carnitine and ascorbic acid affect growth performance, carcass yield and composition, abdominal fat and plasma L-carnitine concentration of broiler chicks reared under normal and high temperature. During the experiment, two temperature regimes were employed in two experimental rooms, which were identical but different in environmental temperature. The regimes were thermoneutral (20-22°C for 24 h) or recycling hot (34-36°C for 8 h and 20-22°C for 16 h). One-day-old broiler chicks (ROSS) were used in the experiment. A 2 x 2 x 2 factorial arrangement was employed with two levels (0 and 50 mg/kg) of supplemental L-carnitine and two levels (0 or 500 mg/kg) of supplemental ascorbic acid in drinking water under thermoneutral or high temperature regimes. Body weight gain was affected by high temperature. However, body weight gain was significantly improved in animals receiving supplemental L-carnitine, ascorbic acid or L-carnitine + ascorbic acid compared to animals receiving unsupplemented diet under high temperature. On the other hand, supplemental L-carnitine or L-carnitine + ascorbic acid reduced body weight gain under thermoneutral condition. Supplemental ascorbic acid significantly improved feed conversion efficiency, the improvement was relatively greater under high temperature. The L-carnitine content in the plasma was higher in the groups receiving supplemental L-carnitine and ascorbic acid under high temperature, while broilers fed supplemental L-carnitine and ascorbic acid had a decreased level of plasma L-carnitine concentration under normal temperature. It is concluded that dietary supplemental L-carnitine or L-carnitine + ascorbic acid may have positive effects on body weight gain, carcass weight under high temperature conditions.     

Mapping the interactions between Escherichia coli TolQ transmembrane segments

The tolQRAB-pal operon is conserved in Gram-negative genomes. The TolQRA proteins of Escherichia coli form an inner membrane complex in which TolQR uses the proton-motive force to regulate TolA conformation and the in vivo interaction of TolA C-terminal region with the outer membrane Pal lipoprotein. The stoichiometry of the TolQ, TolR, and TolA has been estimated and suggests that 4-6 TolQ molecules are associated in the complex, thus involving interactions between the transmembrane helices (TMHs) of TolQ, TolR, and TolA. It has been proposed that an ion channel forms at the interface between two TolQ and one TolR TMHs involving the TolR-Asp(23), TolQ-Thr(145), and TolQ-Thr(178) residues. To define the organization of the three TMHs of TolQ, we constructed epitope-tagged versions of TolQ. Immunodetection of in vivo and in vitro chemically cross-linked TolQ proteins showed that TolQ exists as multimers in the complex. To understand how TolQ multimerizes, we initiated a cysteine-scanning study. Results of single and tandem cysteine substitution suggest a dynamic model of helix interactions in which the hairpin formed by the two last TMHs of TolQ change conformation, whereas the first TMH of TolQ forms intramolecular interactions.     

Mutational analyses define helix organization and key residues of a bacterial membrane energy-transducing complex

In Gram-negative bacteria, many biological processes are coupled to inner membrane ion gradients. Ions transit at the interface of helices of integral membrane proteins, generating mechanical energy to drive energetic processes. To better understand how ions transit through these channels, we used a model system involved in two different processes, one of which depends on inner membrane energy. The Tol machinery of the Escherichia coli cell envelope is dedicated to maintaining outer membrane stability, a process driven by the proton-motive force. The Tol system is parasitized by bacterial toxins called colicins, which are imported through the outer membrane using an energy-independent process. Herein, we mutated TolQ and TolR transmembrane residues, and we analyzed the mutants for outer membrane stability, colicin import and protein complex formation. We identified residues involved in the assembly of the complex, and a new class of discriminative mutations that conferred outer membrane destabilization identical to a tol deletion mutant, but which remained fully sensitive to colicins. Further genetic approaches revealed transmembrane helix interactions and organization in the bilayer, and suggested that most of the discriminative residues are located in a putative aqueous ion channel. We discuss a model for the function of related bacterial molecular motors.     

Patients’ preferences for osteoporosis drug treatment: a discrete-choice experiment

Introduction

The patient’s perspective is becoming increasingly important in clinical and policy decisions. In this study, we aimed to evaluate the preferences of patients with, or at risk of, osteoporosis for medication attributes, and to establish how patients trade between these attributes.

Methods

A discrete choice experiment survey was designed and patients were asked to choose between two hypothetical unlabelled drug treatments (and an opt-out option) that vary in five attributes: efficacy in reducing the risk of fracture, type of potential common side-effects, mode and frequency of administration and out-of-pocket costs. An efficient experimental design was used to construct the treatment option choice sets and a mixed logit panel data model was used to estimate patients’ preferences and trade-offs between attributes.

Results

A total of 257 patients with, or at risk of, osteoporosis completed the experiment. As expected, patients preferred treatment with higher effectiveness and lower cost. They also preferred either an oral monthly tablet or 6-month subcutaneous injection above weekly oral tablets, 3-month subcutaneous, 3-month intravenous or yearly intravenous injections. Patients disliked being at risk of gastro-intestinal disorders more than being at risk of skin reactions and flu-like symptoms. There was significant variation in preferences across the sample for all attributes except subcutaneous injection.

Conclusions

This study revealed that osteoporotic patients preferred 6-month subcutaneous injection and oral monthly tablet, and disliked gastro-intestinal disorders. Moreover, patients were willing to pay a personal contribution or to trade treatment efficacy for better levels of other attributes. Preferences for treatment attributes varied across patients and this highlights the importance of clinical decision-making taking individual preferences into account to improve osteoporosis care.     

The provision of supplementary fresh water improves the breeding success of the globally threatened Northern Bald Ibis Geronticus eremita

The Northern Bald Ibis Geronticus eremita is a globally threatened species with its main remaining world population breeding in an area of sea cliffs and coastal semi‐desert steppe near Agadir in southern Morocco. Between 1998 and 2002, we showed experimentally that the small‐scale provision of fresh water near the breeding colonies led to an increase in the productivity of the birds. The increase was greatest in years with low natural rainfall but was positive in all years tested. The supplementary fresh water appears to help buffer productivity against the impacts of low rainfall and its provision is now part of the ongoing conservation measures for this species.