Use of ribozymes and antisense oligodeoxynucleotides to investigate mechanisms of drug resistance

Chemotherapy can cure a number of human cancers but resistance (either intrinsic or acquired) remains a significant problem in many patients and in many types of solid tumour. Combination chemotherapy (using drugs with different cellular targets/mechanisms) was introduced in order to kill cells which had developed resistance to a specific drug, and to allow delivery of a greater total dose of anti-cancer chemicals by combining drugs with different side-effects (Pratt et al., 1994). Nearly all anti-cancer drugs kill tumour cells by activating an endogenous bio-chemical pathway for cell suicide, known as programmed cell death or apoptosis. This revised version was published online in August 2006 with corrections to the Cover Date.     

Castes in humivorous and litter-dwelling neotropical nasute termites (Isoptera,Termitidae)

Summary The developmental pathways of the neuter castes were studied in three species of Nasutitermitinae from central Panama. The humivorousSubulitermes denisae andCoatitermes clevelandi display several primitive traits: absence of sex dimorphism, representation of both sexes among workers and soldiers, and occurrence of successive worker instars. The litter-dwellingVelocitermes barrocoloradensis has a more complex caste system: female larvae are larger than males and give rise to the large workers, which constitute the bulk of the work force; male larvae proceed to soldiers through a small worker or a special larval instar. The resulting soldier caste is polymorphic. These results support previously formulated hypotheses regarding a link between humivorous diet and reduced polymorphism on the one hand, and between forest-floor foraging and large continuous size variation among soldiers on the other. Whereas the caste systems ofSubulitermes andCoatitermes probably represent a primitive condition,Velocitermes shares derived traits withNasutitermes and the other fully nasute genera previously studied. I therefore hypothesize that ancestors with these advanced features may have spread from the neotropics and be at the origin of most nasute genera, including humivorous taxa, present in other regions.     

Development of non-reproductive castes in the neotropical termite generaCornitermes,Embiratermes andRhynchotermes (Isoptera,Nasutitermitinae)

Summary The developmental pattern of the neuter castes was studied in the mandibulate nasute generaCornitermes, Embiratermes andRhynchotermes. InCornitermes walkeri, all the workers and soldiers are male. There are two larval and a single worker instar. Workers can molt into presoldiers. InEmbiratermes chagresi andRhynchotermes perarmatus, both sexes are present among the neuters. A slight sexual dimorphism (males > females) is discernible among both larval instars and among workers ofE. chagresi; female workers can molt into presoldiers. InR. perarmatus, the sexual dimorphism is conspicuous from the first larval instar on. Male larvae go through two instars, then give rise to workers, which do not molt. InR. perarmatus, there is no worker stage in females, but a third larval instar, preceding the presoldier. Hypotheses are proposed as to the evolution of these caste patterns, attempting to conciliate present knowledge of Nasutitermitinae phylogeny and known evolutionary trends affecting termite caste patterns, according to the species' ecology.Research Associate: National Fund for Scientific Research (Belgium).     

COMPARTMENTATION AND LABELLING OF AMINO ACIDS IN THE DEVELOPING RAT BRAIN AFTER INJECTION OF [U-14C]RIBOSE

Abstract— [U-¹⁴C]Ribose was given by subcutaneous injection to young rats aged 2–56 days. During the first week after birth ¹⁴C in the brain was found mainly combined in glucose, fructose and sedoheptulose which contained 46–57 per cent of the ¹⁴C in the acid soluble metabolites in the rat brain. In contrast, during the critical period (10–15 days after birth) the ¹⁴C in the free sugars decreased from 24 to 3 per cent, while the ¹⁴C content of amino acids in the brain increased from 11 to 44 per cent of the total perchloric acid-soluble ¹⁴C. The increase in labelling of amino acids during the critical period was attributed to increased glycolysis and increased oxidation of pyruvate. The relative specific radioactivity of y -aminobutyrate and aspartate in the rat brain at 28 days after birth was equal to or greater than the relative specific radioactivity of glutamate. Assuming that the increase in amino acid content following the cessation of cell proliferation in the brain is located mainly in cell processes (cytoplasm of axons, dendrites, glial processes and nerve terminals), tentative values were estimated for the pool sizes of glutamate, glutamine, aspartate and y -amino butyrate.     

Qualitative study of decisions about infant feeding among women in east end of London

ObjectiveTo improve understanding of how first time mothers who belong to a socioeconomic group with particularly low rates of breast feeding decide whether or not to initiate breast feeding.DesignQualitative semistructured interviews early in pregnancy and 6-10 weeks after birth.SettingWomen’s homes in east end of London.Subjects21 white, low income women expecting their first baby were interviewed mostly at home, often with their partner or a relative. Two focus groups were conducted.ResultsWomen who had regularly seen a relative or friend successfully breast feed and described this experience positively were more confident about and committed to breast feeding. They were also more likely to succeed. Exposure to breast feeding, however, could be either a positive or a negative influence on the decision to breast feed, depending on the context. Women who had seen breast feeding only by a stranger often described this as a negative influence, particularly if other people were present. All women knew that breast feeding has health benefits. Ownership of this knowledge, however, varied according to the woman’s experience of seeing breast feeding.ConclusionsThe decision to initiate breast feeding is influenced more by embodied knowledge gained from seeing breast feeding than by theoretical knowledge about its benefits. Breast feeding involves performing a practical skill, often with others present. The knowledge, confidence, and commitment necessary to breast feed may be more effectively gained through antenatal apprenticeship to a breastfeeding mother than from advice given in consultations or from books.

Key messages

• Women who have seen successful breast feeding as part of their daily lives and perceive this as a positive experience are more likely to initiate breast feeding
• Embodied knowledge gained through seeing breast feeding may be more influential than theoretical knowledge about the health benefits for women of lower social class
• Listening to pregnant women talking about breast feeding could help clinicians assess the relative importance of theoretical and embodied knowledge for each woman
• Women hoping to breast feed but with little exposure to breast feeding may benefit from an antenatal apprenticeship with a breastfeeding mother
• Ideally apprenticeship would be with a breastfeeding mother from her social network to minimise the potential barriers of embarrassment and lack of confidence with strangers

     

Cell tracing reveals a dorsoventral lineage restriction plane in the mouse limb bud mesenchyme

Regionalization of embryonic fields into independent units of growth and patterning is a widespread strategy during metazoan development. Compartments represent a particular instance of this regionalization, in which unit coherence is maintained by cell lineage restriction between adjacent regions. Lineage compartments have been described during insect and vertebrate development. Two common characteristics of the compartments described so far are their occurrence in epithelial structures and the presence of signaling regions at compartment borders. Whereas Drosophila compartmental organization represents a background subdivision of embryonic fields that is not necessarily related to anatomical structures, vertebrate compartment borders described thus far coincide with, or anticipate, anatomical or cell-type discontinuities. Here, we describe a general method for clonal analysis in the mouse and use it to determine the topology of clone distribution along the three limb axes. We identify a lineage restriction boundary at the limb mesenchyme dorsoventral border that is unrelated to any anatomical discontinuity, and whose lineage restriction border is not obviously associated with any signaling center. This restriction is the first example in vertebrates of a mechanism of primordium subdivision unrelated to anatomical boundaries. Furthermore, this is the first lineage compartment described within a mesenchymal structure in any organism, suggesting that lineage restrictions are fundamental not only for epithelial structures, but also for mesenchymal field patterning. No lineage compartmentalization was found along the proximodistal or anteroposterior axes, indicating that patterning along these axes does not involve restriction of cell dispersion at specific axial positions.     

Mutant Cells That Do Not Respond to Interleukin-1 (IL-1) Reveal a Novel Role for IL-1 Receptor-Associated Kinase

Mutagenized human 293 cells containing an interleukin-1 (IL-1)-regulated herpes thymidine kinase gene, selected in IL-1 and gancyclovir, have yielded many independent clones that are unresponsive to IL-1. The four clones analyzed here carry recessive mutations and represent three complementation groups. Mutant A in complementation group I1 lacks IL-1 receptor-associated kinase (IRAK), while the mutants in the other two groups are defective in unknown components that function upstream of IRAK. Expression of exogenous IRAK in I1A cells (I1A-IRAK) restores their responsiveness to IL-1. Neither NFkappaB nor Jun kinase is activated in IL-1-treated I1A cells, but these responses are restored in I1A-IRAK cells, indicating that IRAK is required for both. To address the role of the kinase activity of IRAK in IL-1 signaling, its ATP binding site was mutated (K239A), completely abolishing kinase activity. In transfected I1A cells, IRAK-K239A was still phosphorylated upon IL-1 stimulation and, surprisingly, still complemented all the defects in the mutant cells. Therefore, IRAK must be phosphorylated by a different kinase, and phospho-IRAK must play a role in IL-1-mediated signaling that does not require its kinase activity.     

Philopatric reproduction, a prime mover in the evolution of termite sociality?

Summary: Philopatric reproduction commonly occurs even in the most basic isopteran lineages and is almost certainly a primitive potentiality of these insects. Several authors hypothesized that opportunities for philopatric reproduction may have been a prime mover for the three most remarkable events in the evolution of termite sociality: the origin of helping behaviour, the origin of soldiers, and the origin of a permanently apterous worker caste. A critical assessment of these hypotheses and a review of relevant evidence are presented here. I first discuss the hypothesis that termite helpers derive from individuals choosing to postpone dispersal because of nest inheritance prospects. Such individuals would have developed helping as a strategy yielding indirect reproductive benefits while they wait for reproductive opportunities. However, it appears that prospects of philopatric reproduction need not be invoked to explain the origin of helping behaviour, which can be justified more parsimoniously by a favourable intrinsic benefit/cost ratio. Second, the hypothesis that soldiers originated through selection for fighting abilities among neotenic reproductives is found to face important difficulties, the major one being how to explain the absence of fighting devices in almost all present-day neotenics. Finally, the hypothesized link between apterism and chances of philopatric reproduction, which might have favoured the onset of the worker caste, is poorly supported by empirical evidence. It appears thus that philopatric reproduction, notwithstanding its importance in the biology of many extant termite species, is unlikely to have been a prime mover in the evolution of helping and of altruistic castes in termites.