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     

Synthesis,Biological Evaluation,and Molecular Docking of Novel Thiazoles and [1,3,4]Thiadiazoles Incorporating Sulfonamide Group as DHFR Inhibitors

2‐(1‐{4‐[(4‐Methylphenyl)sulfonamido]phenyl}ethylidene)thiosemicarbazide ( 3 ) was exploited as a starting material for the synthesis of two novel series of 5‐arylazo‐2‐hydrazonothiazoles 6a  –  6j and 2‐hydrazono[1,3,4]thiadiazoles 10a  –  10d , incorporating sulfonamide group, through its reactions with appropriate hydrazonoyl halides. The structures of the newly synthesized products were confirmed by spectral and elemental analyses. Also, the antimicrobial, anticancer, and DHFR inhibition potency for two series of thiazoles and [1,3,4]thiadiazoles were evaluated and explained by molecular docking studies and SAR analysis.     

Antibacterial activity of polyphenolic compounds isolated from plants of Geraniaceae and Rosaceae families

Polyphenolic compounds present in extracts of plants belonging to the families Geraniaceae (blood-red cranesbill, wood cranesbill, meadow cranesbill, and alfilaria) and Rosaceae (red raspberry, European dewberry, and tormentil) have been tested for their activity against gram-positive and gram-negative bacteria of the genera Azotobacter, Bacillus, and Pseudomonas. The bacteriostatic activity exhibited some species-related features and depended on the polarity of the extracting agent. The bacteriostatic activity of plant-derived phenolic compounds correlated with their antioxidant potential. The plants of the families Geraniaceae and Rosaceae offer promise as a source of raw material for isolation of polyphenolic compounds exhibiting bactericidal activity, including against opportunistic pathogens (B. cereus, E. coli, P. aeruginosa, and S. aureus strains).     

Evaluation of the role of uniparental disomy in early embryolethality of man

We carried out systematic studies of the contribution of uniparental disomy for eight human chromosomes, 2, 9, 11, 15, 16, 19, 20, and 21, to the etiology of spontaneous mortality of human embryos. Most of these chromosomes have regions with orthologous imprinted genes syntenic with those on mouse chromosomes, the disturbed expression of which is related to embryolethality in mice. Screening of uniparental disomy in spontaneous 5- to 16-week abortuses was performed by evaluation of the pattern of inheritance of alleles of polymorphic microsatellite loci located in the studied chromosomes. A total of 100 human embryos with cytogenetically determined normal karyotype were studied, in which arrest at the early stages of intrauterine development was determined by ultrasound examination of pregnant women. During this study, 13 embryos were discarded due to karyotype anomalies or nonpaternity. No cases of uniparental disomy were found among the 87 studied abortuses for any of chromosomes studied. The analysis of the results of this study and four other studies concerning the search for uniparental disomy in dead embryos and fetuses did not reveal its elevated frequency in spontaneous abortuses as compared to the theoretically expected value based on evaluation of the probable combination of meiotic errors in human gametes. The data we obtained suggest that, first, uniparental disomies for human chromosomes that have regions with orthologous imprinted genes syntenic with mouse chromosomes do not contribute noticeably to the death of human embryos at the early developmental stages and, second, the mechanisms underlying embryolethality as a result of disturbed expression of imprinted loci differ markedly in mammals evolutionarily remote from one other.     

Effect of protein deficiency in the female rat diet during pregnancy and lactation on the activity of the membrane and soluble forms of digestive enzymes in the offspring small intestine

Protein deficiency in female rats diet during pregnancy and lactation resulted in deceleration of induction of sucrase both forms in the jejunum and ileum; in acceleration of induction of the maltase membrane from in the jejunum; and in suppression of the lactase membrane form in the ileum; in earlier forming of the adult-type distribution of activity of the membrane form of intestinal alkaline phosphatase and in a decrease in activity of the enzyme soluble form. The findings are corroborated by a suppression of activities of the membrane and soluble forms of the small intestine digestive enzymes in 30-day old rat pups fed with a control (adequate) ration starting 21 days after the birth.     

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.     

The trace fossil Nummipera eocenica from the Tatra Mountains,Poland: morphology and palaeoenvironmental implications

Jach, R., Machaniec, E. & Uchman, A. 2011: The trace fossil Nummipera eocenica from the Tatra Mountains, Poland: morphology and palaeoenvironmental implications. Lethaia, Vol. 45, pp. 342–355. The tubular trace fossil Nummipera eocenica Hölder 1989 occurs in a single stratigraphical horizon in Eocene nummulitic limestones of the Tatra Mountains, Poland. The wall of N. eocenica is built of Discocyclina and Nummulities (larger foraminifera) tests, very rarely of the Ditrupa (Polychaeta) tube fragments, bivalve shell fragments, echinoid spines and coralline algae. Morphotype are distinguished on the basis of wall composition and structure. Morphotype A is dominated by fusiform Discocyclina tests, which were preferentially selected by the trace makers for construction of a well‐constructed and resistant wall. Morphotype B contains more robust tests of Nummulites, while morphotype C is dominated by saddle‐shaped tests of Discocyclina. Nummipera eocenica was produced during a period of seafloor stabilization caused by a deepening. The succession of the morphotypes B, A reflects diminishing energy and increasing water depth. Probably morphotype C represents even lower energy environment than morphotype A. The trace fossil is interpreted as a domichnion, which wall was constructed for protection. The trace maker can be considered between polychaetes and crustaceans; however, comparisons to the closest recent analogues, the polychaete Diopatra cuprea or alpheid shrimps, are not satisfactory. □Bartonian, burrow, Carpathians, large foraminifera, trace fossils.     

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.