PAPP‐A: a new anti‐aging target?

This article focuses on the role of PAPP‐A in mammalian aging. It introduces PAPP‐A and a little of its history, briefly discusses the function of PAPP‐A in the insulin‐like growth factor (IGF) system and the regulators of PAPP‐A expression, and then reviews data concerning PAPP‐A in aging and age‐related diseases especially in regard to the PAPP‐A knockout (KO) mouse. The PAPP‐A KO mouse is a valuable new model to test hypotheses concerning the control of the tissue availability of IGF, independent from systemic levels, on healthspan as well as lifespan.     

Obesity and triple‐negative‐breast‐cancer: Is apelin a new key target?

Epidemiological studies have shown that obese subjects have an increased risk of developing triple‐negative breast cancer (TNBC) and an overall reduced survival. However, the relation between obesity and TNBC remains difficult to understand. We hypothesize that apelin, an adipokine whose levels are increased in obesity, could be a major factor contributing to both tumour growth and metastatization in TNBC obese patients. We observed that development of obesity under high‐fat diet in TNBC tumour‐bearing mice significantly increased tumour growth. By showing no effect of high‐fat diet in obesity‐resistant mice, we demonstrated the necessity to develop obesity‐related disorders to increase tumour growth. Apelin mRNA expression was also increased in the subcutaneous adipose tissue and tumours of obese mice. We further highlighted that the reproduction of obesity‐related levels of apelin in lean mice led to an increased TNBC growth and brain metastases formation. Finally, injections of the apelinergic antagonist F13A to obese mice significantly reduced TNBC growth, suggesting that apelinergic system interference could be an interesting therapeutic strategy in the context of obesity and TNBC.     

Post-fire mortality and water relations of three congeneric shrub species under extreme water stress — a trade-off with fecundity?

Mortality and water relations of three cooccurringHakea species were studied over the first year following a wildfire in scrub-health in southwestern Australia.Hakea ruscifolia regenerated from both resprouting adults and seedlings, whereasH. smilacifolia andH. polyanthema regenerated only from seedlings. We monitored seedling and resprout survival relative to pre-fire numbers and water relations (shoot water potential, transpiration, pressure-volume parameters) in order to determine the relationship between plant mortality and water relations over the critical first summer drought. Seedlings ofH. polyanthema (few initial seedlings per parent) showed little mortality (8%), achieved through both drought avoidance (low transpiration, high predawn water potential and relative water content (RWC), substantial osmotic adjustment) and drought tolerance later in the season. Seedlings ofH. smilacifolia andH. ruscifolia (high seedling/parent ratios) showed little drought avoidance and high mortality (54–68%). The remaining seedlings spent 3–4 months in a wilted condition (up to 3.6 MPa and 45% RWC below the turgor loss point inH. ruscifolia) indicating marked drought tolerance of the survivors. In contrast to its seedlings,H. ruscifolia resprouts were successful drought avoiders and experienced no mortality. The high level of survival and drought resistance ofH. polyanthema was consistent with its large seedlings (via large seeds) and low initial fecundity. The study highlights the importance of the interaction between ecophysiology-morphology and demography in determining the recruitment strategies of plants.     

Host‐cell lipid rafts: a safe door for micro‐organisms?

The lipid raft hypothesis proposed that these microdomains are small (10–200 nM), highly dynamic and enriched in cholesterol, glycosphingolipids and signalling phospholipids, which compartmentalize cellular processes. These membrane regions play crucial roles in signal transduction, phagocytosis and secretion, as well as pathogen adhesion/interaction. Throughout evolution, many pathogens have developed mechanisms to escape from the host immune system, some of which are based on the host membrane microdomain machinery. Thus lipid rafts might be exploited by pathogens as signalling and entry platforms. In this review, we summarize the role of lipid rafts as players in the overall invasion process used by different pathogens to escape from the host immune system.     

Germline stem cell maintenance as a proximate mechanism of life‐history trade‐offs?

We suggest that the commonly observed trade-offs between early- and late-life reproduction may be mediated by genetic variation in germline stem cell maintenance. Stem cell biology provides a natural framework and experimental methods for understanding the mechanistic basis of life-history evolution. At the same time, natural variation in life-history strategies can serve as a powerful tool for identifying the genes and molecular pathways involved in the maintenance of stem cells in aging adults. We illustrate the connections between life-history and stem cells with examples drawn primarily from Drosophila melanogaster and Caenorhabditis elegans, and suggest a number of testable hypotheses and avenues for future investigation that can be addressed with existing models and tools.     

Biometry of Cenomanian–Turonian placoliths: a proxy for changes of fertility and surface‐water temperature?

Most publications discussing Cenomanian–Turonian calcareous nannofossils focus on abundance fluctuations across the boundary interval. So far, there have been no studies that deal with the influence of palaeoenvironmental changes on the size of common Cenomanian–Turonian nannofossil taxa. The genera Biscutum, Broinsonia, Prediscosphaera, Retecapsa and Watznaueria have therefore been analysed from 19 samples of Cenomanian–Turonian age from the Goban Spur, northeast Atlantic. The genus Biscutum shows a slight decrease of mean length from 4.14 μm in the Cenomanian to 3.94 μm in the Turonian. Broinsonia is marked by a decrease from 6.07 μm in the Cenomanian to 5.64 μm in the Turonian. On the other hand, Prediscospheara increases in size from 4.98 μm in the Cenomanian to 5.61 μm in the Turonian. Two genera (Retecapsa, Watznaueria) show no significant changes in their mean length. The mean size of Biscutum is perhaps controlled by nutrients, where larger specimens may have preferred the more fertile palaeoenvironment of the Late Cenomanian. The size decrease of Biscutum in the Turonian is probably related to reduced nutrient availability. The genus Prediscosphaera spp., may have favoured low‐fertility conditions, as its mean size increases in the Turonian. A worldwide decline of the frequency of Broinsonia spp. during the Cenomanian–Turonian transition implies that this genus is not solely controlled by the nutrient content. The size of Broinsonia spp. may have been therefore influenced by the latest Cenomanian warming event. The increase in sea‐surface temperature may have been unfavourable for Broinsonia spp. as reflected by decreasing mean size and frequency. □Calcareous nannofossils, biometry, morphometry, Oceanic Anoxic Event 2.     

Distinct profiles of human B cell effector cytokines: a role in immune regulation?

There is growing interest in the fundamental roles that B cells may play in regulating immune responses. Emerging animal studies point to an important contribution of B cell effector cytokines to immune modulation, yet little is known about the factors regulating such cytokine production. We report that the profile of human B cell cytokine production is context dependent, being critically influenced by the balance of signals through the B cell receptor and CD40. B cells appropriately stimulated by sequential B cell receptor and CD40 stimulation proliferate and secrete TNF-alpha, lymphotoxin, and IL-6, which can act not only as autocrine growth and differentiation factors, but also serve to amplify the ongoing immune response. In contrast, CD40 stimulation alone, a mimic of a B cell receiving bystander T cell help in the absence of specific Ag recognition, induces negligible proinflammatory cytokines, but significant production of IL-10 that serves to suppress inappropriate immune responses. We thus describe a novel paradigm of reciprocal regulation of B cell effector cytokines, and ascribe active roles for human B cells in either promoting or suppressing local immune responses through context-dependent cytokine production.     

Comparative analysis of microRNAs and putative target genes in hybrid clone <Emphasis Type="Italic">Paulownia</Emphasis> ‘yuza 1’ under drought stress

Drought stress in plants often leads to reduced productivity and limited geographic distribution, which can affect human life and ecosystems. The responses of diploid and tetraploid Paulownia tomentosa × Paulownia fortunei to drought have been reported, but the effects of drought stress on the levels of microRNA (miRNA) expression have not been published so far. Here, we constructed four small RNA (sRNA) libraries and four corresponding degradome libraries of well-watered and severe drought-treated diploid and tetraploid plants to identify the miRNAs and their putative target genes in Paulownia ‘yuza 1’, a P. tomentosa × P. fortunei hybrid clone, by sRNA and degradome sequencing. The putative target genes of miRNAs were annotated with gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Three conserved and 21 novel miRNAs responsive to drought stress were found, in which 15 were identified as the main drought responsive miRNAs that conferred higher resistance in tetraploid than in diploid of Paulownia ‘yuza 1’. Our results will lay the foundation for investigating the roles of miRNAs in Paulownia and other trees in response to drought.     

SIRT1 longevity factor suppresses NF‐κB ‐driven immune responses: regulation of aging via NF‐κB acetylation?

The aging process involves changes in immune regulation, i.e. adaptive immunity declines whereas innate immunity becomes activated. NF-kappaB signaling is the master regulator of the both immune systems. Two recent articles highlight the role of the NF-kappaB system in aging and immune responses. Adler et al showed that the NF-kappaB binding domain is the genetic regulatory motif which is most strongly associated with the aging process. Kwon et al studying HIV-1 infection and subsequent immune deficiency process demonstrated that HIV-1 Tat protein binds to SIRT1 protein, a well-known longevity factor, and inhibits the SIRT1-mediated deacetylation of the p65 component of the NF-kappaB complex. As a consequence, the transactivation efficiency of the NF-kappaB factor was greatly potentiated, leading to the activation of immune system and later to the decline of adaptive immunity. These observations support the scenario where immune responses and aging process can be enforced by the potentiation of NF-kappaB transactivation efficiency. Longevity factors, such as SIRT1 and its activators, might regulate the efficiency of the NF-kappaB signaling, the major outcome of which is inflamm-aging via proinflammatory responses.     

Axial‐to‐radial water permeability of leaf major veins: a possible determinant of the impact of vein embolism on leaf hydraulics?

The leaf hydraulic conductance (K_L) was measured in Prunus laurocerasus L. and Juglans regia L. in which previous measurements had revealed different impacts of dehydration on K_L. Leaves of P. laurocerasus lost 8% of their K_L at water potentials (Ψ_L) of ?2.0 MPa. Leaflets of J. regia showed K_L losses of 40% at Ψ_L = ?1.0 MPa. When major veins were blocked using cyanoacrylate to simulate their embolism, the K_L of P. laurocerasus was reduced by 57% but that of J. regia leaflets was reduced by 80%. Such differences were hypothesized to be due to different axial‐to‐radial permeabilites of major veins. Infiltration of leaves with Phoxine B revealed that P. laurocerasus major veins were largely leaky in the radial direction whereas those of J. regia leaflets showed prevailing axial water transport. Differences between species in terms of axial‐to‐radial water permeability were confirmed by measurements of changes of hydraulic resistance along the midrib. The two hydraulic models are discussed in terms of leaf vulnerability to embolism and plant adaptation to dry habitats.     

Assessment of unanticipated unintended effects of genetically modified plants on non‐target organisms: a controversy worthy of pursuit?

A typical risk hypothesis addressed during the environmental risk assessment (ERA) of genetically modified (GM) plants for cultivation is that the novel traits intentionally introduced into GM plants do not adversely affect non‐target organisms (NTOs). However, genetic modification may potentially also lead to unintended changes in the GM plant which could raise safety concerns. Therefore, the European Food Safety Authority (EFSA) advocates the characterization of ecological interactions between the GM plant and representative NTOs as part of the ERA of GM plants for cultivation in the European Union. Yet, this requirement is not unanimously accepted by stakeholders. Here, we present EFSA's approach to assess potential adverse effects on NTOs and summarize some of the stakeholders' views, mostly opposing EFSA's position on scientific grounds.     

The male fight‐flight response: A result of SRY regulation of catecholamines?

The SRY gene, which is located on the Y chromosome and directs male development, may promote aggression and other traditionally male behavioural traits, resulting in the fight-or-flight reaction to stress.     

Does Bt rice pose risks to non‐target arthropods? Results of a meta‐analysis in China

Transgenic Bt rice expressing the insecticidal proteins derived from Bacillus thuringiensis Berliner (Bt) has been developed since 1989. Their ecological risks towards non‐target organisms have been investigated; however, these studies were conducted individually, yielding uncertainty regarding potential agroecological risks associated with large‐scale deployment of Bt rice lines. Here, we developed a meta‐analysis of the existing literature to synthesize current knowledge of the impacts of Bt rice on functional arthropod guilds, including herbivores, predators, parasitoids and detritivores in laboratory and field studies. Laboratory results indicate Bt rice did not influence survival rate and developmental duration of herbivores, although exposure to Bt rice led to reduced egg laying, which correctly predicted their reduced abundance in Bt rice agroecosystems. Similarly, consuming prey exposed to Bt protein did not influence survival, development or fecundity of predators, indicating constant abundances of predators in Bt rice fields. Compared to control agroecosystems, parasitoid populations decreased slightly in Bt rice cropping systems, while detritivores increased. We draw two inferences. One, laboratory studies of Bt rice showing effects on ecological functional groups are mainly either consistent with or more conservative than results of field studies, and two, Bt rice will pose negligible risks to the non‐target functional guilds in future large‐scale Bt rice agroecosystems in China.