Programmed anuclear cell death delimits platelet life span

Platelets are anuclear cytoplasmic fragments essential for blood clotting and wound healing. Despite much speculation, the factors determining their life span in the circulation are unknown. We show here that an intrinsic program for apoptosis controls platelet survival and dictates their life span. Pro-survival Bcl-x(L) constrains the pro-apoptotic activity of Bak to maintain platelet survival, but as Bcl-x(L) degrades, aged platelets are primed for cell death. Genetic ablation or pharmacological inactivation of Bcl-x(L) reduces platelet half-life and causes thrombocytopenia in a dose-dependent manner. Deletion of Bak corrects these defects, and platelets from Bak-deficient mice live longer than normal. Thus, platelets are, by default, genetically programmed to die by apoptosis. The antagonistic balance between Bcl-x(L) and Bak constitutes a molecular clock that determines platelet life span: this represents an important paradigm for cellular homeostasis, and has profound implications for the diagnosis and treatment of disorders that affect platelet number and function.     

The classical complement cascade mediates CNS synapse elimination

During development, the formation of mature neural circuits requires the selective elimination of inappropriate synaptic connections. Here we show that C1q, the initiating protein in the classical complement cascade, is expressed by postnatal neurons in response to immature astrocytes and is localized to synapses throughout the postnatal CNS and retina. Mice deficient in complement protein C1q or the downstream complement protein C3 exhibit large sustained defects in CNS synapse elimination, as shown by the failure of anatomical refinement of retinogeniculate connections and the retention of excess retinal innervation by lateral geniculate neurons. Neuronal C1q is normally downregulated in the adult CNS; however, in a mouse model of glaucoma, C1q becomes upregulated and synaptically relocalized in the adult retina early in the disease. These findings support a model in which unwanted synapses are tagged by complement for elimination and suggest that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative disease.     

Geographic variation and plasticity to water and nutrients in Pelargonium australe

Here, patterns of phenotypic plasticity and trait integration of leaf characteristics in six geographically discrete populations of the perennial herb Pelargonium australe were compared. It was hypothesized that populations would show local adaptation in trait means, but similar patterns of plasticity and trait integration. Further, it was questioned whether phenotypic plasticity was positively correlated with environmental heterogeneity and whether plasticity for water-use traits in particular was adaptive. Seedlings were grown in a glasshouse at six combinations of water and nutrient availability. Leaf anatomical, morphological and gas exchange traits were measured. High amounts of plasticity in leaf traits were found in response to changes in growth conditions and there was evidence of local adaptation among the populations. While there were significant correlations between plasticity and environmental heterogeneity, not all were positive. Notably, patterns of plasticity and trait integration varied significantly among populations. Despite that variation, some of the observed plasticity was adaptive: fitness was correlated with conservative water use when water was limiting. Pelargonium arrived in Australia approximately 5 million yr ago. It is concluded here that high amounts of plasticity, in some cases adaptive, and weak integration among traits may be key to the spread and success of this species.     

Dietary calcium supplementation to lower blood lead levels in pregnancy and lactation

Pregnancy and lactation are states known to be accompanied by physiologically up regulated bone resorption in response to the calcium demands of the developing fetus and nursing infant. The role of calcium supplements in altering maternal responses to fetal demand for calcium is not fully understood. Exposure to the toxicant lead is known to pose a major hazard to fetal neurodevelopment and growth. Since >95% of maternal lead is stored in the bone, mobilization of cumulative maternal lead stores into the circulation represents an endogenous source of exposure, which may pose a significant hazard for the fetus and infant. Maternal dietary calcium supplementation has been associated with reductions in lead levels in both animal and human studies when administered during pregnancy and lactation. Therefore, supplementation of the maternal diet with calcium may represent an important secondary prevention strategy aimed not only at reducing circulating levels of lead in the mother but also at reducing lead exposure to the developing fetus and nursing infant.     

Sensory adaptation

Adaptation occurs in a variety of forms in all sensory systems, motivating the question: what is its purpose? A productive approach has been to hypothesize that adaptation helps neural systems to efficiently encode stimuli whose statistics vary in time. To encode efficiently, a neural system must change its coding strategy, or computation, as the distribution of stimuli changes. Information theoretic methods allow this efficient coding hypothesis to be tested quantitatively. Empirically, adaptive processes occur over a wide range of timescales. On short timescales, underlying mechanisms include the contribution of intrinsic nonlinearities. Over longer timescales, adaptation is often power-law-like, implying the coexistence of multiple timescales in a single adaptive process. Models demonstrate that this can result from mechanisms within a single neuron.     

Cytoskeleton and cell wall function in penetration resistance

Plants successfully repel the vast majority of potential pathogens that arrive on their surface, with most microorganisms failing to breach the outer epidermal wall. Resistance to penetration at the epidermis is a key component of basal defence against disease and critically depends on fortification of the cell wall at the site of attempted penetration through the development of specialised cell wall appositions rich in antimicrobial compounds. Formation of cell wall appositions is achieved by rapid reorganisation of actin microfilaments, actin-dependent transport of secretory products to the infection site and local activation of callose synthesis. Plants are finely tuned to detect the presence of pathogens on their surface, perceiving both chemical and physical signals of pathogen origin. In the on-going evolution of interaction strategies, plants must continually monitor and out manoeuvre pathogen avoidance or suppression of plant defences in order to preserve the effectiveness of penetration resistance.     

How accurately is ncRNA aligned within whole-genome multiple alignments?

Background  

Multiple alignment of homologous DNA sequences is of great interest to biologists since it provides a window into evolutionary processes. At present, the accuracy of whole-genome multiple alignments, particularly in noncoding regions, has not been thoroughly evaluated.