A Ralstonia solanacearum type III effector alters the actin and microtubule cytoskeleton to promote bacterial virulence in plants.

Cellular responses to biotic stress frequently involve signaling pathways that are conserved across eukaryotes. These pathways include the cytoskeleton, a proteinaceous network that senses external cues at the cell surface and signals to interior cellular components. During biotic stress, dynamic cytoskeletal rearrangements serve as a platform from which early immune-associated processes are organized and activated.

Getting to the root of Ralstonia invasion.

Plant diseases caused by soilborne pathogens are a major limiting factor in crop production. Bacterial wilt disease, caused by soilborne bacteria in the Ralstonia solanacearum Species Complex (Ralstonia), results in significant crop loss throughout the world. Ralstonia invades root systems and colonizes plant xylem, changing plant physiology and ultimately causing plant wilting in susceptible varieties.

Tomato deploys defence and growth simultaneously to resist bacterial wilt disease.

Plant disease limits crop production, and host genetic resistance is a major means of control. Plant pathogenic Ralstonia causes bacterial wilt disease and is best controlled with resistant varieties. Tomato wilt resistance is multigenic, yet the mechanisms of resistance remain largely unknown.

Candidate Effector Proteins from the Maize Tar Spot Pathogen Localize to Diverse Plant Cell Compartments.

Most fungal pathogens secrete effector proteins into host cells to modulate their immune responses, thereby promoting pathogenesis and fungal growth. One such fungal pathogen is the ascomycete , which causes tar spot disease on leaves of maize (). Sequencing of the genome revealed 462 putatively secreted proteins, of which 40 contain expected effector-like sequence characteristics.

Effectors Localize to Diverse Organelles in Hosts.

Phytopathogenic bacteria secrete type III effector (T3E) proteins directly into host plant cells. T3Es can interact with plant proteins and frequently manipulate plant host physiological or developmental processes. The proper subcellular localization of T3Es is critical for their ability to interact with plant targets, and knowledge of T3E localization can be informative for studies of effector function.

Investigation of exenatide elimination and its in vivo and in vitro degradation.

Exenatide is a 39 amino acid incretin mimetic for the treatment of type 2 diabetes, with glucoregulatory activity similar to glucagon-like peptide-1 (GLP-1). Exenatide is a poor substrate for the major route of GLP-1 degradation by dipeptidyl peptidase-IV, and displays enhanced pharmacokinetics and in vivo potency in rats relative to GLP-1. The kidney appears to be the major route of exenatide elimination in the rat.

Ex vivo human placental transfer of the peptides pramlintide and exenatide (synthetic exendin-4).

Two peptides, pramlintide (37 amino acids), an analog of human amylin, and exenatide, synthetic exendin-4 (39 amino acids), are both in late-stage clinical development as potential new treatments for people with diabetes. Both are potential long-term treatments, and there is the likelihood that some women will become pregnant while using one of these peptide therapies. Therefore, it was important to evaluate the potential for each peptide to cross the placental barrier and thereby result in exposure to the fetus.

Safety, toxicokinetics and tissue distribution of long-term intravenous liposomal amphotericin B (AmBisome): a 91-day study in rats.

Purpose: Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated.

Methods: Rats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery.

Safety and toxicokinetics of intravenous liposomal amphotericin B (AmBisome) in beagle dogs.

Purpose: Amphotericin B (AmB) in small, unilamellar liposomes (AmBisome) has an improved therapeutic index, and altered pharmacokinetics. The repeat-dose safety and toxicokinetic profiles of AmBisome were studied at clinically relevant doses.

Methods: Beagle dogs (5/sex/group) received intravenous AmBisome (0.

Toxicological profile and pharmacokinetics of a unilamellar liposomal vesicle formulation of amphotericin B in rats.

AmBisome (ABLP) is a unilamellar liposomal preparation of amphotericin B that has demonstrated an improved safety profile compared to conventional amphotericin B. Single- and multiple-dose pharmacokinetics were determined by using noncompartmental methods for rats administered ABLP at 1, 3, 9, and 20 mg/kg/day. The toxicological profile was evaluated following 30 consecutive days of intravenous ABLP administration.

Retinoblastoma, melanoma and the atypical mole syndrome.

Retinoblastoma patients and their relatives appear to have an increased risk of other cancers, especially melanoma, which represents 7% of second primaries in retinoblastoma survivors. Individuals belonging to families with the atypical mole syndrome (another family cancer syndrome with a genetic susceptibility to melanoma) have a recognizable phenotype, with many atypical melanocytic naevi. We report two families in which both retinoblastoma and melanoma occurred.

Inhalation toxicity of aerosolized pentamidine isethionate in rats and dogs.

The toxicity of inhaled aerosolized pentamidine isethionate solutions in rats and dogs was evaluated. Nose-only exposure equipment and a mass mean aerodynamic particle size of < or = 2 microns were employed. Rats received either a single inhaled dose estimated at 0, 1.

Pharmacology and toxicology of chronically infused epidural clonidine.HCl in dogs.

To evaluate the physiological effects and toxicity of epidural clonidine.HCl, male Beagle dogs were prepared with chronic lumbar epidural catheters and administered constant infusions of either saline (N = 10), or 80 micrograms/hr (N = 6), 200 micrograms/hr (N = 6), or 320 micrograms/hr (N = 12) clonidine.HCl at a rate of 4 ml/24 hr for 28 days.

Subchronic (13-week) toxicity studies of N,N-dimethylaniline administered to Fischer 344 rats and B6C3F1 mice.

The subchronic toxicity of N,N-dimethylaniline (DMA) was studied by administration in corn oil by gavage at doses of 31.25, 62.5, 125, 250, 20, or 500 mg/kg body weight to groups of 10 male and 10 female F344 rats and B6C3F1 mice 5 d per week for 13 wk.

The sanctity of the upper lid in lower eyelid reconstruction questioned. A modification of a lid sharing procedure with a long-term follow-up.

Sharing techniques using the upper eyelid to reconstruct the lower one have been criticised for causing distortion of the normal upper lid leading to corneal exposure and possible visual disturbance, and for creating second-rate lids. A modification of previously described tarsoconjunctival flap techniques is described which minimises the known complications of earlier methods. A flap of conjunctiva alone is mobilised from the upper eyelid and covered with a full thickness skin graft.

Clinical diagnostic accuracy in the management of primary Stage I cutaneous malignant melanoma in a plastic surgery unit.

In a retrospective review of 614 primary Stage I cutaneous malignant melanomata and 40 nonmelanoma lesions, the diagnostic accuracy(DA) for malignant melanoma was 86.2%. A positive preoperative clinical diagnosis of malignant melanoma was confirmed histologically in 564/604 (93.