Continuous intravenous infusion in athymic (nude) rats: an animal model for evaluating the efficacy of anti-cancer agents

The athymic (nude) rat (rnu/rnu) has been used for a number of years in research into various human tumours involving xenotransplantation. We now report the validation of a continuous intravenous infusion method in nude rats using a tail cuff tether, which enables the study of the efficacy of novel anti-cancer materials in this mutant strain, using intravenous infusion and with no restriction of the animals or of the tumour implantation sites by jackets. Ten animals each had a cannula surgically implanted into the vena cava via the femoral vein and exteriorized via a tail cuff. Animals were housed singly in conventional cages following surgery. Following a recovery period of 5 days all animals were continuously infused with physiological saline at an infusion rate of 0.5 ml/h for a further 37 days. Body weights and food consumption were recorded weekly. Blood samples were taken approximately 14 days post-surgery and analysed for haematology and clinical chemistry parameters. All animals were successfully cannulated, and no unexpected adverse clinical signs were noted during the recovery period and the 37 days of infusion. The results demonstrate that it is possible to surgically cannulate the femoral vein of athymic (nude) rats and infuse them in conventional cages for a period of up to 37 days with minimal adverse effects. The minimal restraint required provides benefits both to the animal and to the conduct of studies such as assessment of tumour growth in the absence of a jacket. Recent work has demonstrated that the same techniques can be successfully applied to the nude mouse.     

Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction

Free pedicled transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction is often advocated as the procedure of choice for autogenous tissue breast reconstruction in high-risk patients, such as smokers. However, whether use of the free TRAM flap is a desirable option for breast reconstruction in smokers is still unclear. All patients undergoing breast reconstruction with free TRAM flaps at our institution between February of 1989 and May of 1998 were reviewed. Patients were classified as smokers, former smokers (patients who had stopped smoking at least 4 weeks before surgery), and nonsmokers. Flap and donor-site complications in the three groups were compared. Information on demographic characteristics, body mass index, and comorbid medical conditions was used to perform multivariate statistical analysis. A total of 936 breast reconstructions with free TRAM flaps were performed in 718 patients (80.9 percent immediate; 23.3 percent bilateral). There were 478 nonsmokers, 150 former smokers, and 90 smokers. Flap complications occurred in 222 (23.7 percent) of 936 flaps. Smokers had a higher incidence of mastectomy flap necrosis than nonsmokers (18.9 percent versus 9.0 percent; p = 0.005). Smokers who underwent immediate reconstruction had a significantly higher incidence of mastectomy skin flap necrosis than did smokers who underwent delayed reconstruction (21.7 percent versus 0 percent; p = 0.039). Donor-site complications occurred in 106 (14.8 percent) of 718 patients. Donor-site complications were more common in smokers than in former smokers (25.6 percent versus 10.0 percent; p = 0.001) or nonsmokers (25.6 percent versus 14.2 percent; p = 0.007). Compared with nonsmokers, smokers had significantly higher rates of abdominal flap necrosis (4.4 percent versus 0.8 percent; p = 0.025) and hernia (6.7 percent versus 2.1 percent; p = 0.016). No significant difference in complication rates was noted between former smokers and nonsmokers. Among smokers, patients with a smoking history of greater than 10 pack-years had a significantly higher overall complication rate compared with patients with a smoking history of 10 or fewer pack-years (55.8 percent versus 23.8 percent; p = 0.049). In summary, free TRAM flap breast reconstruction in smokers was not associated with a significant increase in the rates of vessel thrombosis, flap loss, or fat necrosis compared with rates in nonsmokers. However, smokers were at significantly higher risk for mastectomy skin flap necrosis, abdominal flap necrosis, and hernia compared with nonsmokers. Patients with a smoking history of greater than 10 pack-years were at especially high risk for perioperative complications, suggesting that this should be considered a relative contraindication for free TRAM flap breast reconstruction. Smoking-related complications were significantly reduced when the reconstruction was delayed or when the patient stopped smoking at least 4 weeks before surgery.     

Closure of hemicorporectomy with bilateral subtotal thigh flaps

Hemicorporectomy is typically performed with a circumferential truncal incision, and the wound is closed primarily. Wound disruption is a common complication, especially at the base of the wound closure and posteriorly at the lumbar vertebral level. We report a case of the use of bilateral subtotal thigh flaps for the closure of a hemicorporectomy wound in a patient with a defect extending up to the high lumbar region. The subtotal thigh flap is a well-vascularized thick flap that provides a firm support for the abdominal viscera and is a large flap that can be used to close even a high lumbar defect.     

From inclusive fitness to fixation probability in homogeneous structured populations

The methods of inclusive fitness provide a powerful analysis of the action of selection on social behaviour. The key component of this analysis is the concept of relatedness R. In infinite populations, a standard method of calculating relatedness coefficients is through coefficients of consanguinity using the notion of genetic identity by descent. In this paper, we show that this approach can also be made to work in finite populations and we assume here that the population has a homogeneous structure, such as an island model. We demonstrate that, under the assumption that genetic effects are small and additive, the resulting formulation of inclusive fitness is equivalent to other significant measures of selection in finite populations, including the change in average allele frequency and fixation probability. The results are illustrated for a model of the evolution of cooperation in a finite island population.     

Signal transduction network motifs and biological memory

Memory is a ubiquitous phenomenon in biological systems, yet the mechanisms responsible for memory, and how to manipulate it at the subcellular level, remain poorly understood. Subjected to transient stimuli, biological systems can exhibit short early responses and/or prolonged (or permanent) late responses. Experimental evidence suggests that early responses (short-term memory) involve post-translational modification of existing proteins and/or their intracellular relocalization, whereas late responses (long-term memory) depend on new protein synthesis. Although this provides an intuitive explanation at the basic molecular level, it does little to clarify the important dynamics that actually maintain memory at the systems level. In this study, we use mathematical modeling to study dynamical mechanisms of biological memory. We first examined the response of four fundamental motifs (positive/negative feedforward and feedback) to external stimuli. Because motifs do not exist in isolation within the cell, we then combined these motifs to form signaling modules to understand how they confer biological memory. These motifs, and different combinations thereof, displayed distinct behavior in response to external stimuli. The principles described in this study have important implications for experimental approaches to identify the mechanisms for biological memory and for the development of therapeutic strategies to modulate signaling network responses in the setting of human disease.     

Can predation by invasive mice drive seabird extinctions?

The house mouse, Mus musculus, is one of the most widespread and well-studied invasive mammals on islands. It was thought to pose little risk to seabirds, but video evidence from Gough Island, South Atlantic Ocean shows house mice killing chicks of two IUCN-listed seabird species. Mouse-induced mortality in 2004 was a significant cause of extremely poor breeding success for Tristan albatrosses, Diomedea dabbenena (0.27 fledglings/pair), and Atlantic petrels, Pterodroma incerta (0.33). Population models show that these levels of predation are sufficient to cause population decreases. Unlike many other islands, mice are the only introduced mammals on Gough Island. However, restoration programmes to eradicate rats and other introduced mammals from islands are increasing the number of islands where mice are the sole alien mammals. If these mouse populations are released from the ecological effects of predators and competitors, they too may become predatory on seabird chicks.     

Minimum reporting standards for plant biology context information in metabolomic studies

Plant metabolomics has matured over the past 8 years. Plant biologists routinely use comprehensive analyses of plant metabolites to discover new responses to genetic or environmental perturbation, or to validate initial hypotheses on the function and in vivo action of gene products. The wealth of scientific findings has increasingly provoked interest to share and review raw or processed data from plant metabolomics reports. We here suggest a minimum of parameters to be reported in order to define details of experimental study designs in plant metabolomics studies.     

Construction of a high-density,high-resolution genetic map and its integration with BAC-based physical map in channel catfish

Construction of genetic linkage map is essential for genetic and genomic studies. Recent advances in sequencing and genotyping technologies made it possible to generate high-density and high-resolution genetic linkage maps, especially for the organisms lacking extensive genomic resources. In the present work, we constructed a high-density and high-resolution genetic map for channel catfish with three large resource families genotyped using the catfish 250K single-nucleotide polymorphism (SNP) array. A total of 54,342 SNPs were placed on the linkage map, which to our knowledge had the highest marker density among aquaculture species. The estimated genetic size was 3,505.4 cM with a resolution of 0.22 cM for sex-averaged genetic map. The sex-specific linkage maps spanned a total of 4,495.1 cM in females and 2,593.7 cM in males, presenting a ratio of 1.7 : 1 between female and male in recombination fraction. After integration with the previously established physical map, over 87% of physical map contigs were anchored to the linkage groups that covered a physical length of 867 Mb, accounting for ∼90% of the catfish genome. The integrated map provides a valuable tool for validating and improving the catfish whole-genome assembly and facilitates fine-scale QTL mapping and positional cloning of genes responsible for economically important traits.