DISTORTED2 encodes an ARPC2 subunit of the putative Arabidopsis ARP2/3 complex

Arabidopsis trichomes are unicellular, branched structures that have highly constrained requirements for the cytoskeleton. The 'distorted group' genes function downstream from microtubule-based branch initiation, and are required during the actin-dependent phase of polarized stalk and branch expansion. Of the eight known 'distorted group' genes, a subset encode homologs of ARP2/3 complex subunits. In eukaryotic cells, the seven-protein ARP2/3 complex nucleates actin filament networks that push on the plasma membrane and organelles. In plants cells, the existence and function of an ARP2/3 complex is unclear. In this paper, we report that DISTORTED2 (DIS2) encodes a paralogue of the ARP2/3 complex subunit ARPC2. DIS2 has ARPC2 activity, based on its ability to rescue the growth defects of arpc2 (arc35Delta) null yeast cells. Like known ARPC2s, DIS2 physically interacts with ARPC4. Mutations in DIS2 cause a distorted trichome phenotype, defects in cell-cell adhesion, and a modest reduction in shoot FW. The actin cytoskeleton in dis2 trichomes is extensive, but developing branches fail to generate and maintain highly organized cytoplasmic actin bundles.     

Synthesis of Aldehydo-sugar Derivatives of Pyrazoloquinoline as Inhibitors of Herpes Simplex Virus Type 1 Replication

Synthesis of a novel series of structurally related pyrazoloquinoline nucleosides is described. All the newly synthesized compounds were examined for their in vitro antiviral activity against herpes simplex type-1 as shown by two different bioassays, namely; crystal violet staining or the MTS tetrazolium dye measurement. The acute toxicity (LD50) values of the biologically active compounds were determined.     

Genetic diversity assessment of summer squash landraces using molecular markers

Plant identification, classification, and genotyping within a germplasm collection are essential elements for establishing a breeding program that enhances the probability of plants with desirable characteristics in the market place. In this study, random amplified polymorphic DNA (RAPD) was used as a molecular tool to assess the diversity and relationship among 20 summer squash (Curcubita pepo L.) landraces traditionally used to treat hypertension and prostate hyperplasia. A total of 10 RAPD primers produced 65 reproducible bands of which 46 (70.77 %) were polymorphic, indicating a large number of genotypes within the summer squash lines. Cluster analysis divided the summer squash germplasm into two groups, one including one landrace and a second containing 19 landraces that could be divided into five sub-groups. Results of this study indicate the potential of RAPD markers for the identification and assessment of genetic variations among squash landraces and provide a number of choices for developing a successful breeding program to improve summer squash.     

A multiyear survey of helminths from wild saddleback (Leontocebus weddelli) and emperor (Saguinus imperator) tamarins

The establishment of baseline data on parasites from wild primates is essential to understand how changes in habitat or climatic disturbances will impact parasite–host relationships. In nature, multiparasitic infections of primates usually fluctuate temporally and seasonally, implying that the acquisition of reliable data must occur over time. Individual parasite infection data from two wild populations of New World primates, the saddleback (Leontocebus weddelli) and emperor (Saguinus imperator) tamarin, were collected over 3 years to establish baseline levels of helminth prevalence and parasite species richness (PSR). Secondarily, we explored variation in parasite prevalence across age and sex classes, test nonrandom associations of parasite co‐occurrence, and assess the relationship between group size and PSR. From 288 fecal samples across 105 individuals (71 saddleback and 34 emperor tamarins), 10 parasite taxa were identified by light microscopy following centrifugation and ethyl‐acetate sedimentation. Of these taxa, none were host‐specific, Dicrocoeliidae and Cestoda prevalences differed between host species, Prosthenorchis and Strongylida were the most prevalent. Host age was positively associated with Prosthenorchis ova and filariform larva, but negatively with cestode and the Rhabditoidea ova. We detected no differences between expected and observed levels of co‐infection, nor between group size and parasite species richness over 30 group‐years. Logistic models of individual infection status did not identify a sex bias; however, age and species predicted the presence of four and three parasite taxa, respectively, with saddleback tamarins exhibiting higher PSR. Now that we have reliable baseline data for future monitoring of these populations, next steps involve the molecular characterization of these parasites, and exploration of linkages with health parameters.     

Polycyclic Aromatic Hydrocarbons (PAHs) in Surface Sediments of Lake Manzala,Egypt

This investigation represents the first extensive study of the spatial distribution, sources, and potential effects of polycyclic aromatic hydrocarbons (PAHs) in sediments from Lake Manzala, the largest of Egypt's Mediterranean coastal lakes. The concentrations of PAHs (Σ39 components) ranged from 246 to 9910 ng g^?1 dry wt., the highest values corresponding to urban hotspots with high anthropogenic input coming from wastewater discharges and combustion activities and decreasing offshore. The levels of PAHs were significantly lower compared to values reported in several coastal/estuarine areas (e.g., in Spain, Italy, USA, and Egypt) receiving substantial anthropogenic inputs from urban and industrial activities. Source ratios indicated that the PAHs were mainly from petrogenic sources in near-shore urban hotspots, with higher contributions of pyrolytic sources in coastal and offshore areas which are little influenced by human activities. Sediment quality guidelines (SQGs) showed that except at one station heavily impacted by sewage discharge, the total and individual PAH concentrations were below effect range low (ERL) concentrations that are not likely to adversely affect benthic biota.     

TgGRA23, a novel Toxoplasma gondii dense granule protein associated with the parasitophorous vacuole membrane and intravacuolar network

Toxoplasma gondii is an intracellular protozoan parasite, which relies on a specialized compartment, the parasitophorous vacuole (PV), to survive within host cells. Dense granules within the parasite release a large variety of proteins to maintain the integrity of the vacuole structure. Here, we identified a novel dense granule protein in T. gondii, TgGRA23, which is a homolog of the Sarcocystis muris dense granule protein, SmDG32. Recombinant TgGRA23 (rTgGRA23) expressed in Escherichia coli as a glutathione S-transferase (GST) fusion protein was used to raise antisera in mice and rabbits. Immunoblotting showed that antisera from the immunized mice and rabbits reacted with parasite lysates to yield a 21-kDa native protein. In addition, immuno-electron microscopic examination showed that TgGRA23 resides in the dense granules, PV membrane and intravacuolar network of the parasite. To confirm the precise subcellular localization of TgGRA23 in T. gondii, an immunofluorescent antibody test was performed using dense granule markers. Notably, TgGRA23 co-localized with other dense granule proteins including TgGRA4 and TgGRA7, in the extracellular-stage parasites. Biochemical experiments indicated that TgGRA23 is insoluble and may form an electrostatic complex that is resistant to non-ionic detergents. Furthermore, specific antibodies to TgGRA23 were detected during the chronic stage of Toxoplasma infection in mice. Our results suggest that TgGRA23 is an as yet unknown member of the T. gondii dense granule proteins, and that it may be involved in remodeling or maintenance of the PV.     

Synthesis of some pyrazolyl benzenesulfonamide derivatives as dual anti-inflammatory antimicrobial agents

Four series of pyrazolylbenzenesulfonamide derivatives were synthesized and evaluated for their anti-inflammatory activity using cotton pellet induced granuloma and carrageenan-induced rat paw edema bioassays. Moreover, COX-1 and COX-2 inhibitory activity, ulcerogenic effect and acute toxiCIT000y were also determined. Furthermore, the target compounds were screened for their in-vitro antimicrobial activity against Eischerichia coli, Staphylococcus aureus and Candida albicans. Compounds 4-(3-Phenyl-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide 9a and 4-(3-Tolyl-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide 9b were not only found to be the most active dual anti-inflammatory antimicrobial agents in the present study with good safety margin and minimal ulcerogenic effect but also exhibited good selective inhibitory activity towards COX-2. A docking pose for 9a and 9b separately in the active site of the human COX-2 enzyme was also obtained. Therefore, these compounds would represent a fruitful matrix for the development of dual anti-inflammatory antimicrobial candidates with remarkable COX-2 selectivity.     

Synthesis,anti-inflammatory,cytotoxic, and COX-1/2 inhibitory activities of cyclic imides bearing 3-benzenesulfonamide,oxime, and β-phenylalanine scaffolds: a molecular docking study

Abstract

Cyclic imides containing 3-benzenesulfonamide, oxime, and β-phenylalanine derivatives were synthesised and evaluated to elucidate their in vivo anti-inflammatory and ulcerogenic activity and in vitro cytotoxic effects. Most active anti-inflammatory agents were subjected to in vitro COX-1/2 inhibition assay. 3-Benzenesulfonamides (2–4, and 9), oximes (11–13), and β-phenylalanine derivative (18) showed potential anti-inflammatory activities with 71.2–82.9% oedema inhibition relative to celecoxib and diclofenac (85.6 and 83.4%, respectively). Most active cyclic imides 4, 9, 12, 13, and 18 possessed ED₅₀ of 35.4–45.3?mg kg^?1 relative to that of celecoxib (34.1?mg kg^?1). For the cytotoxic evaluation, the selected derivatives 2–6 and 8 exhibited weak positive cytotoxic effects (PCE = 2/59–5/59) at 10?μM compared to the standard drug, imatinib (PCE = 20/59). Cyclic imides bearing 3-benzenesulfonamide (2–5, and 9), acetophenone oxime (11–14, 18, and 19) exhibited high selectivity against COX-2 with SI > 55.6–333.3 relative to that for celecoxib [SI > 387.6]. β-Phenylalanine derivatives 21–24 and 28 were non-selective towards COX-1/2 isozymes as indicated by their SI of 0.46–0.68.     

Exploring structure-activity relationship of S-substituted 2-mercaptoquinazolin-4(3H)-one including 4-ethylbenzenesulfonamides as human carbonic anhydrase inhibitors

Abstract

Inhibitory action of newly synthesised 4-(2-(2-substituted-thio-4-oxoquinazolin-3(4H)-yl)ethyl)benzenesulfonamides compounds 2–13 against human carbonic anhydrase (CA, EC 4.2.1.1) (hCA) isoforms I, II, IX, and XII, was evaluated. hCA I was efficiently inhibited by compounds 2–13 with inhibition constants (K_Is) ranging from 57.8–740.2?nM. Compounds 2, 3, 4, and 12 showed inhibitory action against hCA II with K_Is between 6.4 and 14.2?nM. CA IX exhibited significant sensitivity to inhibition by derivatives 2–13 with K_I values ranging from 7.1 to 93.6?nM. Compounds 2, 3, 4, 8, 9, and 12 also exerted potent inhibitory action against hCA XII (K_Is ranging from 3.1 to 20.2?nM). Molecular docking studies for the most potent compounds 2 and 3 were conducted to exhibit the binding mode towards hCA isoforms as a promising step for SAR analyses which showed similar interaction with co-crystallized ligands. As such, a subset of these mercaptoquinazolin-4(3H)-one compounds represented interesting leads for developing new efficient and selective carbonic anhydrase inhibitors (CAIs) for the management of a variety of diseases including glaucoma, epilepsy, arthritis and cancer.     

Efficacy of Nile tilapia (Oreochromis niloticus) juveniles and spinosyns bioinsecticides against aquatic stages of Culex pipiens: An experimental study

The mosquito Culex pipiens is the most widely distributed dipteran species in all regions of Egypt and the principal vector of Wuchereria bancrofti and certain arboviruses in human beings. For controlling C. pipiens vector, biological tools (e.g., larvivorous fish and bioinsecticides) are more potent and safer options to the environment, human beings, and beneficial organisms than chemical pesticides. The efficiency of O. niloticus juveniles as predatory fish species and two bioinsecticides, spinosad 24% and spinetoram 12%, was investigated against the C. pipiens developmental stages in the laboratory. The first trial evaluated the predatory efficacy of small-sized O. niloticus (2.1–2.6 cm; 250–315 mg) and large-sized O. niloticus (2.5–3.2 cm; 250–315 mg) against the 3rd larvae and pupae of C. pipiens. This is the first report in Egypt confirming the predation potential of O. niloticus as efficient predatory fish against the immature C. pipiens. Large-sized O. niloticus predated a greater number of 3rd of C. pipiens larvae and pupae than the small-sized ones. Furthermore, the daily consumption of C. pipiens larvae by small- and large-sized O. niloticus was significantly higher than the pupae. The second trial assessed the toxicity efficacy of spinosad 24% and spinetoram 12% against C. pipiens larvae and pupae. The results confirmed that the tested bioinsecticides showed higher potency toward C. pipiens larvae than pupae after exposure for 24 h and 48 h. Spinosad was more toxic toward 3rd C. pipiens larvae (LC₅₀ = 0.013 and 0.003 mg/L) and pupae (LC₅₀ = 320.69 and 44.28 mg/L) than spinetoram after 24 and 48 h. Herein, O. niloticus juveniles (as promising native predatory fish) and spinosyns bioinsecticides were more effective against C. pipiens in the larval stage than in the pupal stage. In conclusion, Nile tilapia juveniles and biorational compounds, spinosad 24% and spinetoram 12%, might be considered as promising and favorable environmental biological agents for controlling C. pipiens in Egypt. However, further trials are needed to investigate the potential of these agents in the control of this mosquito vector under field conditions.