'A mate or a meal' – Pre-gravid behaviour of female Anopheles gambiae from the islands of São Tomé and Príncipe, West Africa

Background

The spread of drug resistance is making malaria control increasingly difficult. Mathematical models for the transmission dynamics of drug sensitive and resistant strains can be a useful tool to help to understand the factors that influence the spread of drug resistance, and they can therefore help in the design of rational strategies for the control of drug resistance.

Methods

We present an epidemiological framework to investigate the spread of anti-malarial resistance. Several mathematical models, based on the familiar Macdonald-Ross model of malaria transmission, enable us to examine the processes and parameters that are critical in determining the spread of resistance.

Results

In our simplest model, resistance does not spread if the fraction of infected individuals treated is less than a threshold value; if drug treatment exceeds this threshold, resistance will eventually become fixed in the population. The threshold value is determined only by the rates of infection and the infectious periods of resistant and sensitive parasites in untreated and treated hosts, whereas the intensity of transmission has no influence on the threshold value. In more complex models, where hosts can be infected by multiple parasite strains or where treatment varies spatially, resistance is generally not fixed, but rather some level of sensitivity is often maintained in the population.

Conclusions

The models developed in this paper are a first step in understanding the epidemiology of anti-malarial resistance and evaluating strategies to reduce the spread of resistance. However, specific recommendations for the management of resistance need to wait until we have more data on the critical parameters underlying the spread of resistance: drug use, spatial variability of treatment and parasite migration among areas, and perhaps most importantly, cost of resistance.     

Three maize root-specific genes are not correctly expressed in regenerated caps in the absence of the quiescent center

The quiescent center is viewed as an architectural template in the root apical meristem of all angiosperm and gymnosperm root tips. In roots of Arabidopsis thaliana (L.) Heynh., the quiescent center inhibits differentiation of contacting initial cells and maintains the surrounding initial cells as stem cells. Here, the role of the quiescent center in the development of the maize (Zea mays L.) root cap has been further explored. Three maize root-specific genes were identified. Two of these were exclusively expressed in the root cap and one of them encoded a GDP-mannose-4,6-dehydratase. Most likely these two genes are structural, tissue-specific markers of the cap. The third gene, a putative glycine-rich cell wall protein, was expressed in the cap and in the root epidermis and, conceivably is a positional marker of the cap. Microsurgical and molecular data indicate that the quiescent center and cap initials may regulate the positional and structural expression of these genes in the cap and thereby control root cap development. Received: 22 September 1999 / Accepted: 9 November 1999     

The influence of aquatic surface respiration (ASR) on cardio-respiratory function of the serrasalmid fish Piaractus mesopotamicus

When exposed to severely hypoxic water, many teleosts skim the better oxygenated surface layer (aquatic surface respiration, ASR). Information is scarce concerning the thresholds triggering ASR and its cardio-respiratory consequences. To assess the ambient conditions leading to ASR and to evaluate its effects on cardio-respiratory function, we exposed specimens of Piaractus mesopotamicus to gradual hypoxia (water oxygen tension ranging from 120 to 10 torr) with or, alternatively, without access to the surface. Concurrently, ASR, cardiac and respiratory frequencies, O₂ uptake and gill ventilation were monitored. With surface access, ASR developed below the critical tension for O₂ uptake (34 torr) by normal gill ventilation. Moreover, the time spent in ASR increased with prolonged hypoxic exposure to a maximum of 95% of total time. Without surface access, the species exhibited hypoxic bradycardia, that had not occurred in the group with fully developed ASR. Even without ASR, P. mesopotamicus recovered readily from hypoxic exposure, showing that this species possesses a number of mechanisms to cope with environmental hypoxia.     

Isolation and characterization of a new non-toxic two-chain ribosome-inactivating protein from fruits of elder (Sambucus nigra L.)

Sambucus (Caprifoliaceae) species contain nigrin b and ebulinI, which are two-chain ribosomeinactivating proteins (RIPs)belonging to a new type of RIPS which are non-toxic to miceand cultured human cells. In this work the presence in fruitsof elder (S. nigra L.) of a new non-toxic type 2 RIP (nigrinf) that co-exists with a lectin known as SNA IV is described.Nigrin f strongly inhibited protein synthesis in mammalian,but not in plant, ribosomes, promoting the depurination of sensitiveribosomes and thus allowing the release of the RIP diagnosticRNA fragment. Nigrin f is composed of two dissimilar subunitslinked by disulphide bridges with apparent M_r values of 31 600and 26 300. The N-terminal amino acid sequence revealed closehomology of the catalytic A chain with type 1 RIPs, especiallythose from Cucurbitaceae, and the B chain with several lectinspreviously isolated from Sambucus species. Nigrin f was nottoxic to mice when injected intraperitoneally up to 2 mg kg^–1.In addition, NHC human cells were also insensitive to nigrinf up to 60 µg ml^–1. Anti-nigrin b rabbit polyclonalantibodies reacted with nigrin f, indicating that nigrin b andnigrin f are proteins with similar structures. Key words: Sambucus nigra, elder fruits, nigrin f, ribosomeinactivating protein, characterization     

Temporal and Spatial Requirement of EMF1 Activity for Arabidopsis Vegetative and Reproductive Development

EMBRYONIC FLOWER （EMF） genes are required to maintain vegetative development via repression of flower homeotic genes in Arabidopsis. Removal of EMF gene function caused plants to flower upon germination, producing abnormal and sterile flowers. The pleiotropic effect of ernfl mutation suggests its requirement for gene programs involved in diverse developmental processes. Transgenic plants harboring EMF1 promoter：：glucuronidase （GUS） reporter gene were generated to investigate the temporal and spatial expression pattern of EMF1. These plants displayed differential GUS activity in vegetative and flower tissues, consistent with the role of EMF1 in regulating multiple gene programs. EMFI：：GUS expression pattern in emf mutants suggests organ-specific auto-regulation. Sense- and antisense （as） EMF1 cDNA were expressed under the control of stage- and tissue-specific promoters in transgenic plants. Characterization of these transgenic plants showed that EMF1 activity is required in meristematic as well as differentiating tissues to rescue emf mutant phenotype. Temporal removal or reduction of EMF1 activity in the embryo or shoot apex of wild-type seedlings was sufficient to cause early flowering and terminal flower formation in adult plants. Such reproductive cell memory is reflected in the flower MADS-box gene activity expressed prior to flowering in these early flowering plants. However, temporal removal of EMF1 activity in flower meristem did not affect flower development. Our results are consistent with EMF1＇s primary role in repressing flowering in order to allow for vegetative growth.     

Engineered bromodomains to explore the acetylproteome

MS‐based analysis of the acetylproteome has highlighted a role for acetylation in a wide array of biological processes including gene regulation, metabolism, and cellular signaling. To date, anti‐acetyllysine antibodies have been used as the predominant affinity reagent for enrichment of acetyllysine‐containing peptides and proteins; however, these reagents suffer from high nonspecific binding and lot‐to‐lot variability. Bromodomains represent potential affinity reagents for acetylated proteins and peptides, given their natural role in recognition of acetylated sequence motifs in vivo. To evaluate their efficacy, we generated recombinant proteins representing all known yeast bromodomains. Bromodomain specificity for acetylated peptides was determined using degenerate peptide arrays, leading to the observation that different bromodomains display a wide array of binding specificities. Despite their relatively weak affinity, we demonstrate the ability of selected bromodomains to enrich acetylated peptides from a complex biological mixture prior to mass spectrometric analysis. Finally, we demonstrate a method for improving the utility of bromodomain enrichment for MS through engineering novel affinity reagents using combinatorial tandem bromodomain pairs.     

Quality Control Test for Sequence-Phenotype Assignments

Relating a gene mutation to a phenotype is a common task in different disciplines such as protein biochemistry. In this endeavour, it is common to find false relationships arising from mutations introduced by cells that may be depurated using a phenotypic assay; yet, such phenotypic assays may introduce additional false relationships arising from experimental errors. Here we introduce the use of high-throughput DNA sequencers and statistical analysis aimed to identify incorrect DNA sequence-phenotype assignments and observed that 10–20% of these false assignments are expected in large screenings aimed to identify critical residues for protein function. We further show that this level of incorrect DNA sequence-phenotype assignments may significantly alter our understanding about the structure-function relationship of proteins. We have made available an implementation of our method at http://bis.ifc.unam.mx/en/software/chispas.     

The Homeodomain Iroquois Proteins Control Cell Cycle Progression and Regulate the Size of Developmental Fields

During development, proper differentiation and final organ size rely on the control of territorial specification and cell proliferation. Although many regulators of these processes have been identified, how both are coordinated remains largely unknown. The homeodomain Iroquois/Irx proteins play a key, evolutionarily conserved, role in territorial specification. Here we show that in the imaginal discs, reduced function of Iroquois genes promotes cell proliferation by accelerating the G1 to S transition. Conversely, their increased expression causes cell-cycle arrest, down-regulating the activity of the Cyclin E/Cdk2 complex. We demonstrate that physical interaction of the Iroquois protein Caupolican with Cyclin E-containing protein complexes, through its IRO box and Cyclin-binding domains, underlies its activity in cell-cycle control. Thus, Drosophila Iroquois proteins are able to regulate cell-autonomously the growth of the territories they specify. Moreover, our results provide a molecular mechanism for a role of Iroquois/Irx genes as tumour suppressors.