Effect of sorghum resistant to Stenodiplosis sorghicola (Coquillett) (Diptera: Cecidomyiidae) on oviposition and development of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae)

Abstract Helicoverpa armigera oviposition preference for, and larval development on sorghum hybrids with differing resistance to sorghum midge, Stenodiplosis sorghicola , were investigated. When H. armigera larvae were fed seed of resistant and susceptible hybrids in the laboratory there were no differences in larval and pupal sizes or the rate of development. The same result was recorded when larvae fed on panicles on plants in a glasshouse. On some sampling occasions, significantly more eggs were laid on panicles of resistant hybrids in the field. This occurred when plants were in plots and also in a mixed planting. Midge-resistance status did not affect levels of egg parasitism. In a field study using recombinant inbred lines between a midge-resistant and a midge-susceptible line, no relationship was found between level of resistance and oviposition of H. armigera . We conclude that, although midge-resistant hybrids are sometimes preferred for oviposition by H. armigera, the resistance per se does not determine this preference. Egg survival, larval survival, development and resultant damage are not significantly affected by the midge-resistance status of the host.     

Progesterone-induced Acrosome Exocytosis Requires Sequential Involvement of Calcium-independent Phospholipase A2β (iPLA2β) and Group X Secreted Phospholipase A2 (sPLA2)

Phospholipase A₂ (PLA₂) activity has been shown to be involved in the sperm acrosome reaction (AR), but the molecular identity of PLA₂ isoforms has remained elusive. Here, we have tested the role of two intracellular (iPLA₂β and cytosolic PLA₂α) and one secreted (group X) PLA₂s in spontaneous and progesterone (P4)-induced AR by using a set of specific inhibitors and knock-out mice. iPLA₂β is critical for spontaneous AR, whereas both iPLA₂β and group X secreted PLA₂ are involved in P4-induced AR. Cytosolic PLA₂α is dispensable in both types of AR. P4-induced AR spreads over 30 min in the mouse, and kinetic analyses suggest the presence of different sperm subpopulations, using distinct PLA₂ pathways to achieve AR. At low P4 concentration (2 μm), sperm undergoing early AR (0–5 min post-P4) rely on iPLA₂β, whereas sperm undergoing late AR (20–30 min post-P4) rely on group X secreted PLA₂. Moreover, the role of PLA₂s in AR depends on P4 concentration, with the PLA₂s being key actors at low physiological P4 concentrations (≤2 μm) but not at higher P4 concentrations (∼10 μm).     

Synthesis and in vitro cytotoxicity of novel long chain busulphan analogues

Two novel long chain alkanediol dimethanesulphonates, analogues of busulphan, were synthesized. Their in vitro cytotoxicity was evaluated against six solid tumor cell lines (A2780, H322, LL, WiDr, C26-10 and UMSCC-22B). 2-Tetradecylbutane-1,4-diol dimethanesulphonate was proved to be the most active compound exhibiting IC50 values between 20.82 and 26.36 microM.     

Synthesis and fluorescence properties of intramolecularly quenched fluorogenic p-nitroanilides containing coumarin or quinolinone derivatives as fluorophores.

Nine model intramolecularly quenched fluorogenic substrates (IQFS) of the general structure F-Phe-NH-Np, containing coumarin or quinolinone derivatives as fluorophores (F) and the p-nitroanilide group (Np) as quencher, were synthesized. The study of the fluorescence properties of the substrates synthesized and the corresponding fluorophores showed that efficient quenching of fluorescence (>89%) was observed in all cases. The combination of 7-glutarylamido-4-methyl-coumarin (Mec-NH-Glt-OH) or 7-methoxy-4-coumaryl-acetic acid (Mca) with the p-nitroanilide group gave the best results (97.2 and 98.8% quenching, respectively). These fluorophores can be used to convert peptide p-nitroanilides into IQFS, which, retaining their chromogenic properties, may be applied in both fluorometric and colorimetric assays.     

Quantification of angiogenesis in estrogen receptor-positive and negative breast carcinoma

Background

The objective of this study was to evaluate angiogenesis according to CD34 antigen expression in estrogen receptor (ER)-positive and negative breast carcinomas.

Methods

This study comprised 64 cases of infiltrating ductal carcinoma in postmenopausal women divided into two groups: Group A: ER-positive, n = 35; and Group B: ER-negative, n = 29. The anti-CD34 monoclonal antibody was used as a marker for endothelial cells. Microvessel count was carried out in 10 fields per slide using a 40× objective lens (magnification 400×). Statistical analysis of the data was performed using Student's t-test (p < 0.05).

Results

The mean number of vessels stained with the anti-CD34 antibody in the estrogen receptor-positive and negative tumors was 23.51 ± 1.15 and 40.24 ± 0.42, respectively. The number of microvessels was significantly greater in the estrogen receptor-negative tumors (p < 0.001).

Conclusion

ER-negative tumors have significantly greater CD34 antigen expression compared to ER-positive tumors.

     

2-Oxoamide inhibitors of phospholipase A2 activity and cellular arachidonate release based on dipeptides and pseudodipeptides

A series of 2-oxoamides based on dipeptides and pseudodipeptides were synthesized and their activities towards two human intracellular phospholipases A₂ (GIVA cPLA₂ and GVIA iPLA₂) and one human secretory phospholipase A₂ (GV sPLA₂) were evaluated. Derivatives containing a free carboxyl group are selective GIVA cPLA₂ inhibitors. A derivative based on the ethyl ester of an ether pseudodipeptide is the first 2-oxoamide, which preferentially inhibits GVIA iPLA₂. The effect of 2-oxoamides on the generation of arachidonic acid from RAW 264.7 macrophages was also studied and it was found that selective GIVA cPLA₂ inhibitors preferentially inhibited cellular arachidonic acid release; one pseudodipeptide gave an IC₅₀ value of 2 μM.     

Synthesis, binding studies and in vivo biological evaluation of novel non-peptide antihypertensive analogues

AT(1) antagonists (SARTANs) constitute the last generation of drugs for the treatment of hypertension, designed and synthesized to mimic the C-terminal segment of the vasoconstrictive hormone angiotensin II (AngII). They exert their action by blocking the binding of AngII on the AT(1) receptor. Up to date eight AT(1) antagonists have been approved for the regulation of high blood pressure. Although these molecules share common structural features and are designed to act under the same mechanism, they have differences in their pharmacological profiles and antihypertensive efficacy. Thus, there is still a need for novel analogues with better pharmacological and financial profiles. An example of a novel synthetic non peptide AT(1) antagonist which devoids the classical template of SARTANs is MM1. In vivo studies showed that MMK molecules, which fall in the same class of MM1, had a significant antihypertensive (40-80% compared to the drug losartan) activity. However, in vitro affinity studies showed that losartan has considerably higher affinity. The theoretical docking studies showed that MM1 acts on the same site of the receptor as losartan. They exert hydrophobic interactions with amino acid Val108 of the third helix of the AT(1) receptor and other hydrophobic amino acids in spatial vicinity. In addition, losartan favours multiple hydrogen bondings between its tetrazole group with Lys199. These additional interactions may in part explain its higher in vitro binding affinity.     

Efficient protocols for the synthesis of enantiopure gamma-amino acids with proteinogenic side chains.

The synthesis of enantiopure gamma-substituted gamma-amino acids with proteinogenic side chains, starting from the corresponding natural alpha-amino acids, was studied. N-Protected amino aldehydes containing various protective groups were prepared from the corresponding amino alcohols by oxidation with NaOCl in the presence of AcNH-TEMPO and directly reacted with methyl, benzyl and tert-butyl phosphoranylidene acetate to produce alpha,beta-unsaturated gamma-amino esters. Simultaneous hydrogenation of the double bond and removal of either the benzyl or benzyloxycarbonyl group led to N- or C-protected gamma-amino acids in high yield. The enantiomeric purity was studied by 1H NMR analysis of Mosher amides and chiral HPLC analysis.