Phage Lambda CIII: A Protease Inhibitor Regulating the Lysis-Lysogeny Decision

The ATP-dependent protease FtsH (HflB) complexed with HflKC participates in post-translational control of the lysis-lysogeny decision of bacteriophage lambda by rapid degradation of lambda CII. Both phage-encoded proteins, the CII transcription activator and the CIII polypeptide, are required for efficient lysogenic response. The conserved CIII is both an inhibitor and substrate of FtsH. Here we show that the protease inhibitor CIII is present as oligomeric amphipathic α helical structures and functions as a competitive inhibitor of FtsH by preventing binding of the CII substrate. We identified single alanine substitutions in CIII that abolish its activity. We characterize a dominant negative effect of a CIII mutant. Thus, we suggest that CIII oligomrization is required for its function. Real-time analysis of CII activity demonstrates that the effect of CIII is not seen in the absence of either FtsH or HflKC. When CIII is provided ectopically, CII activity increases linearly as a function of the multiplicity of infection, suggesting that CIII enhances CII stability and the lysogenic response. FtsH function is essential for cellular viability as it regulates the balance in the synthesis of phospholipids and lipopolysaccharides. Genetic experiments confirmed that the CIII bacteriostatic effects are due to inhibition of FtsH. Thus, the early presence of CIII following infection stimulates the lysogenic response, while its degradation at later times ensures the reactivation of FtsH allowing the growth of the established lysogenic cell

Limits to modern contraceptive use among young women in developing countries: a systematic review of qualitative research

<p>Abstract</p> <p>Background</p> <p>Improving the reproductive health of young women in developing countries requires access to safe and effective methods of fertility control, but most rely on traditional rather than modern contraceptives such as condoms or oral/injectable hormonal methods. We conducted a systematic review of qualitative research to examine the limits to modern contraceptive use identified by young women in developing countries. Focusing on qualitative research allows the assessment of complex processes often missed in quantitative analyses.</p> <p>Methods</p> <p>Literature searches of 23 databases, including Medline, Embase and POPLINE^®, were conducted. Literature from 1970–2006 concerning the 11–24 years age group was included. Studies were critically appraised and meta-ethnography was used to synthesise the data.</p> <p>Results</p> <p>Of the 12 studies which met the inclusion criteria, seven met the quality criteria and are included in the synthesis (six from sub-Saharan Africa; one from South-East Asia). Sample sizes ranged from 16 to 149 young women (age range 13–19 years). Four of the studies were urban based, one was rural, one semi-rural, and one mixed (predominantly rural). Use of hormonal methods was limited by lack of knowledge, obstacles to access and concern over side effects, especially fear of infertility. Although often more accessible, and sometimes more attractive than hormonal methods, condom use was limited by association with disease and promiscuity, together with greater male control. As a result young women often relied on traditional methods or abortion. Although the review was limited to five countries and conditions are not homogenous for all young women in all developing countries, the overarching themes were common across different settings and contexts, supporting the potential transferability of interventions to improve reproductive health.</p> <p>Conclusion</p> <p>Increasing modern contraceptive method use requires community-wide, multifaceted interventions and the combined provision of information, life skills, support and access to youth-friendly services. Interventions should aim to counter negative perceptions of modern contraceptive methods and the dual role of condoms for contraception and STI prevention should be exploited, despite the challenges involved.</p

Global analysis of gene expression in NGF-deprived sympathetic neurons identifies molecular pathways associated with cell death

Developing sympathetic neurons depend on nerve growth factor (NGF) for survival and die by apoptosis after NGF withdrawal. This process requires de novo gene expression but only a small number of genes induced by NGF deprivation have been identified so far, either by a candidate gene approach or in mRNA differential display experiments. This is partly because it is difficult to obtain large numbers of sympathetic neurons for in vitro studies. Here, we describe for the first time, how advances in gene microarray technology have allowed us to investigate the expression of all known genes in sympathetic neurons cultured in the presence and absence of NGF

The Tri-Trophic Interactions Hypothesis: Interactive Effects of Host Plant Quality, Diet Breadth and Natural Enemies on Herbivores

Several influential hypotheses in plant-herbivore and herbivore-predator interactions consider the interactive effects of plant quality, herbivore diet breadth, and predation on herbivore performance. Yet individually and collectively, these hypotheses fail to address the simultaneous influence of all three factors. Here we review existing hypotheses, and propose the tri-trophic interactions (TTI) hypothesis to consolidate and integrate their predictions. The TTI hypothesis predicts that dietary specialist herbivores (as compared to generalists) should escape predators and be competitively dominant due to faster growth rates, and that such differences should be greater on low quality (as compared to high quality) host plants. To provide a preliminary test of these predictions, we conducted an empirical study comparing the effects of plant (Baccharis salicifolia) quality and predators between a specialist (Uroleucon macolai) and a generalist (Aphis gossypii) aphid herbivore. Consistent with predictions, these three factors interactively determine herbivore performance in ways not addressed by existing hypotheses. Compared to the specialist, the generalist was less fecund, competitively inferior, and more sensitive to low plant quality. Correspondingly, predator effects were contingent upon plant quality only for the generalist. Contrary to predictions, predator effects were weaker for the generalist and on low-quality plants, likely due to density-dependent benefits provided to the generalist by mutualist ants. Because the TTI hypothesis predicts the superior performance of specialists, mutualist ants may be critical to A. gossypii persistence under competition from U. macolai. In summary, the integrative nature of the TTI hypothesis offers novel insight into the determinants of plant-herbivore and herbivore-predator interactions and the coexistence of specialist and generalist herbivores

Altered mRNA expression of genes related to nerve cell activity in the fracture callus of older rats: A randomized, controlled, microarray study

BACKGROUND: The time required for radiographic union following femoral fracture increases with age in both humans and rats for unknown reasons. Since abnormalities in fracture innervation will slow skeletal healing, we explored whether abnormal mRNA expression of genes related to nerve cell activity in the older rats was associated with the slowing of skeletal repair. METHODS: Simple, transverse, mid-shaft, femoral fractures with intramedullary rod fixation were induced in anaesthetized female Sprague-Dawley rats at 6, 26, and 52 weeks of age. At 0, 0.4, 1, 2, 4, and 6 weeks after fracture, a bony segment, one-third the length of the femur, centered on the fracture site, including the external callus, cortical bone, and marrow elements, was harvested. cRNA was prepared and hybridized to 54 Affymetrix U34A microarrays (3/age/time point). RESULTS: The mRNA levels of 62 genes related to neural function were affected by fracture. Of the total, 38 genes were altered by fracture to a similar extent at the three ages. In contrast, eight neural genes showed prolonged down-regulation in the older rats compared to the more rapid return to pre-fracture levels in younger rats. Seven genes were up-regulated by fracture more in the younger rats than in the older rats, while nine genes were up-regulated more in the older rats than in the younger. CONCLUSIONS: mRNA of 24 nerve-related genes responded differently to fracture in older rats compared to young rats. This differential expression may reflect altered cell function at the fracture site that may be causally related to the slowing of fracture healing with age or may be an effect of the delayed healing

Chondroitin sulfates and their binding molecules in the central nervous system

Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases

The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration

Apoptosis is a programmed cell death that plays a critical role during the development of the nervous system and in many chronic neurodegenerative diseases, including Alzheimer's disease (AD). This pathology, characterized by a progressive degeneration of cholinergic function resulting in a remarkable cognitive decline, is the most common form of dementia with high social and economic impact. Current therapies of AD are only symptomatic, therefore the need to elucidate the mechanisms underlying the onset and progression of the disease is surely needed in order to develop effective pharmacological therapies. Because of its pivotal role in neuronal cell death, apoptosis has been considered one of the most appealing therapeutic targets, however, due to the complexity of the molecular mechanisms involving the various triggering events and the many signaling cascades leading to cell death, a comprehensive understanding of this process is still lacking. Modular systems biology is a very effective strategy in organizing information about complex biological processes and deriving modular and mathematical models that greatly simplify the identification of key steps of a given process. This review aims at describing the main steps underlying the strategy of modular systems biology and briefly summarizes how this approach has been successfully applied for cell cycle studies. Moreover, after giving an overview of the many molecular mechanisms underlying apoptosis in AD, we present both a modular and a molecular model of neuronal apoptosis that suggest new insights on neuroprotection for this disease