Circulating mutant DNA to assess tumor dynamics

The measurement of circulating nucleic acids has transformed the management of chronic viral infections such as HIV. The development of analogous markers for individuals with cancer could similarly enhance the management of their disease. DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. In this study, we applied a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in 162 plasma samples from 18 subjects undergoing multimodality therapy for colorectal cancer. We found that ctDNA measurements could be used to reliably monitor tumor dynamics in subjects with cancer who were undergoing surgery or chemotherapy. We suggest that this personalized genetic approach could be generally applied to individuals with other types of cancer.     

Interactions Between Chronic Stress and Chronic Consumption of Caffeine on the Enzymatic Antioxidant System

We studied the effect of chronic caffeine on parameters related to oxidative stress in different brain regions of stressed and non-stressed rats. Wistar rats were divided into three groups: control (receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water). These groups were subdivided into non-stressed and stressed (repeated restraint stress during 40 days). Lipid peroxide levels and the total radical-trapping potential were assessed, as well as antioxidant enzyme activities superoxide dismutase, gluthatione peroxidase, and catalase in hippocampus, striatum and cerebral cortex. Results showed interactions between stress and caffeine, especially in the cerebral cortex, since caffeine increased the activity of some antioxidant enzymes, but not in stressed animals. We concluded that chronic administration of caffeine led, in some cases, to increased activity of antioxidant enzymes. However, these effects were not observed in the stressed animals.     

Acquisition and processing of nonhuman primate samples for genetic and phylogenetic analyses

Primates have long been a favorite subject of evolutionary biologists, and in recent decades, have come to play an increasingly important role in biomedical research, including comparative genetics and phylogenetics. The growing list of annotated genome databases from nonhuman primate species is expected to aid in these endeavors, allowing many analyses to be performed partially or even entirely in silico. However, whole genome sequence data are typically derived from only one, or at best a few, individuals. As a consequence, information in the databases does not capture variation within species or populations, nor can the sequence of one individual be taken as representative across all loci. Furthermore, the vast majority of primate species have not been sequenced, and only a small percentage of species are currently slated for whole genome sequencing efforts. Finally, for many species data on patterns and levels of RNA expression will be lacking. Thus, there will continue to be a demand for samples from nonhuman primates as raw material for genetic and phylogenetic analyses. Gathering such samples can be complicated, with many legal and practical barriers to obtaining samples in the field or transporting samples between research centers and across borders. Here, we provide basic but critical advice for those initiating studies requiring genetic material from nonhuman primates, including some guidance on how to locate and obtain samples, brief overviews of common protocols for handling and processing samples, and a table of useful links for locating resources related to the acquisition of samples. We also advocate for the creation of curated banks of nonhuman primate samples, particularly renewable sources of genetic material such as immortalized cell lines or fibroblasts, to reduce the need for repeated or redundant sampling from living animals.     

An improved ontological representation of dendritic cells as a paradigm for all cell types

Background  

Recent increases in the volume and diversity of life science data and information and an increasing emphasis on data sharing and interoperability have resulted in the creation of a large number of biological ontologies, including the Cell Ontology (CL), designed to provide a standardized representation of cell types for data annotation. Ontologies have been shown to have significant benefits for computational analyses of large data sets and for automated reasoning applications, leading to organized attempts to improve the structure and formal rigor of ontologies to better support computation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL's utility for computation and for cross-species data integration.     

Implementation of an insecticide-treated net subsidy scheme under a public-private partnership for malaria control in Tanzania – challenges in implementation

Background

In the past decade there has been increasing visibility of malaria control efforts at the national and international levels. The factors that have enhanced this scenario are the availability of proven interventions such as artemisinin-based combination therapy, the wide scale use of insecticide-treated nets (ITNs) and a renewed emphasis in indoor residual house-spraying. Concurrently, there has been a window of opportunity of financial commitments from organizations such as the Global Fund for HIV/AIDS, Tuberculosis and Malaria (GFATM), the President's Malaria Initiative and the World Bank Booster programme.

Methods

The case study uses the health policy analysis framework to analyse the implementation of a public-private partnership approach embarked upon by the government of Tanzania in malaria control – 'The Tanzania National Voucher Scheme'- and in this synthesis, emphasis is on the challenges faced by the scheme during the pre-implementation (2001 – 2004) and implementation phases (2004 – 2005). Qualitative research tools used include: document review, interview with key informants, stakeholder's analysis, force-field analysis, time line of events, policy characteristic analysis and focus group discussions. The study is also complemented by a cross-sectional survey, which was conducted at the Rufiji Health Demographic Surveillance Site, where a cohort of women of child-bearing age were followed up regarding access and use of ITNs.

Results

The major challenges observed include: the re-introduction of taxes on mosquito nets and related products, procurement and tendering procedures in the implementation of the GFATM, and organizational arrangements and free delivery of mosquito nets through a Presidential initiative.

Conclusion

The lessons gleaned from this synthesis include: (a) the consistency of the stakeholders with a common vision, was an important strength in overcoming obstacles, (b) senior politicians often steered the policy agenda when the policy in question was a 'crisis event', the stakes and the visibility were high, (c) national stakeholders in policy making have an advantage in strengthening alliances with international organizations, where the latter can become extremely influential in solving bottlenecks as the need arises, and (d) conflict can be turned into an opportunity, for example the Presidential initiative has inadvertently provided Tanzania with important lessons in the organization of 'catch-up' campaigns.     

Solution structure and backbone dynamics of the Trypanosoma cruzi cysteine protease inhibitor chagasin

A Trypanosoma cruzi cysteine protease inhibitor, termed chagasin, is the first characterized member of a new family of tight-binding cysteine protease inhibitors identified in several lower eukaryotes and prokaryotes but not present in mammals. In the protozoan parasite T.cruzi, chagasin plays a role in parasite differentiation and in mammalian host cell invasion, due to its ability to modulate the endogenous activity of cruzipain, a lysosomal-like cysteine protease. In the present work, we determined the solution structure of chagasin and studied its backbone dynamics by NMR techniques. Structured as a single immunoglobulin-like domain in solution, chagasin exerts its inhibitory activity on cruzipain through conserved residues placed in three loops in the same side of the structure. One of these three loops, L4, predicted to be of variable length among chagasin homologues, is flexible in solution as determined by measurements of (15)N relaxation. The biological implications of structural homology between chagasin and other members of the immunoglobulin super-family are discussed.     

Mechanical strain to maxillary incisors during direct laryngoscopy

Dexmedetomidine is a highly selective adrenergic receptor agonist, which has a dose-dependent sedative hypnotic effect. Furthermore, it also has pharmacological properties, and the ability to inhibit sympathetic activity and improve cardiovascular stability during an operation. However, its protective effect on patients with severe craniocerebral injury in the perioperative period remains unclear. Eighty adult male SD rats were used and divided into two groups (n = 40, each group): dexmedetomidine injury group (experimental group), and sodium chloride injury group (control group). Models of severe craniocerebral injury were established in these two groups using the modified Feeney’s free-fall method. As soon as the establishment of models was succeed, rat in the experimental group received 1 μg of dexmedetomidine (0.1 ml), while each rat in the control group was given 0.1 ml of 0.9% sodium chloride. Blood was sampled from an incision at the femoral vein to detect TNF-α and IL-2 levels at 1, 12, 24,36,48 and 72 h after establishing the model in the two groups. After severe craniocerebral injury, TNF-α levels of rats were lower in every stage and at different degrees in the experimental group than in the control group (P < 0.05), while IL-2 levels were lower in the experimental group to different extents (P < 0.05). Dexmedetomidine protects the brain of rats with severe craniocerebral injury by reducing the release of inflammatory mediators.     

Patchy bed disturbance and fish predation independently influence the distribution of stream invertebrates and algae

1. The identification of factors determining the patchy distribution of organisms in space and time is a central concern of ecology. Predation and abiotic disturbance are both well-known drivers of this patchiness, but their interplay is still poorly understood, especially for communities dominated by mobile organisms in frequently disturbed ecosystems. 2. We investigated the separate and interactive influences of bed disturbance by floods and predation by fish on the benthic community in a flood-prone stream. Electric fields excluded fish predators from half of 48 stream bed patches (area 0·49 m(2) ) with contrasting disturbance treatments. Three types of bed disturbance were created by either scouring or filling patches to a depth of 15-20 cm or by leaving the patches undisturbed, thus mimicking the mosaic of scour and fill caused by a moderate flood. Benthic invertebrates and algae were sampled repeatedly until 57 days after the disturbance. 3. Disturbance influenced all ten investigated biological response variables, whereas predation affected four variables. Averaged across time, invertebrate taxon richness and total abundance were highest in stable patches. Algal biomass and densities of five of the seven most common invertebrate taxa (most of which were highly mobile) were higher in fill than in scour patches, whereas two taxa were more abundant in scour and stable than in fill patches. Furthermore, two common invertebrate grazers were more abundant and algal biomass tended to be reduced in fish exclusion patches, suggesting a patch-scale trophic cascade from fish to algae. 4. Our results highlight the importance of patchy physical disturbance for the microdistribution of mobile stream organisms and indicate a notable, but less prevalent, influence of fish predation at the patch scale in this frequently disturbed environment. Disturbance and predation treatments interacted only once, suggesting that the observed predation effects were largely independent of local bed disturbance patterns.