PKS2: A link between phototropin signalling and auxin transport - a study on how plants sense and respond to light.

The blue light photoreceptors phototropins (phot1 and phot2 in Arabidopsis thaliana (L.)) carry out various light responses of great adaptive value that optimize plant growth. These processes include phototropism (the bending of an organ induced by unequal light distribution), chloroplast movements, stomatal opening, leaf flattening and solar tracking. The biochemical pathways controlling these important blue light responses are just starting to be elucidated. The PHYTOCHROME KINASE SUBSTRATE (PKS1-4) proteins - the subject of this research - have recently been identified as novel phototropism signalling components. PKS1 (the founding member of this family) interacts in a same complex in vivo with phot1 and the important phot1 signalling element NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3). This suggested that the PKS may act as early components of phot signalling. This work further investigates the role of this protein family during phototropin signalling Genetic experiments clearly showed that the PKS do not control chloroplast movements or stomatal opening. However, PKS2 plays a critical role with NPH3 during leaf flattening and solar tracking. Epistasis data indicated that both proteins act in phot1 and phot2 pathways, which is consistent with their in vivo interaction with both phototropins. Because phototropism, leaf flattening and solar tracking are developmental processes regulated by the hormone auxin, the role of PKS2 and NPH3 during auxin homeostasis was also investigated. Interestingly, PKS2 loss-of-function restores leaf flattening in the auxin transporter mutant aux1. Moreover, PKS2 and NPH3 are found in a same complex with AUX1 in vivo. Taken together, these results suggest that PKS2 may act with NPH3 as a connecting point between phot signalling and auxin transport. Further experiments were performed to explore the molecular mode of action of PKS2 and NPH3 in this process. The significance of these results is discussed.

Sense and antisense transcripts in the histone H1 (HIS-1) locus of Leishmania major.

Histone H1 in the parasitic protozoan Leishmania is a developmentally regulated protein encoded by two genes, HIS-1.1 and HIS-1.2. These genes are separated by approximately 20 kb of sequence and are located on the same DNA strand of chromosome 27. When Northern blots of parasite RNA were probed with HIS-1 strand-specific riboprobes, we detected sense and antisense transcripts that were polyadenylated and developmentally regulated. When the HIS-1.2 coding region was replaced with the coding region of the neomycin phosphotransferase gene, antisense transcription of this gene was unaffected, indicating that the regulatory elements controlling antisense transcription were located outside of the HIS-1.2 gene, and that transcription in Leishmania can occur from both DNA strands even in the presence of transcription of a selectable marker in the complementary strand. A search for other antisense transcripts within the HIS-1 locus identified an additional transcript (SC-1) within the intervening HIS-1 sequence, downstream of adenine and thymine-rich sequences. These results show that gene expression in Leishmania is not only regulated polycistronically from the sense strand of genomic DNA, but that the complementary strand of DNA also contains sequences that could drive expression of open reading frames from the antisense strand of DNA. These findings suggest that the parasite has evolved in such a way as to maximise the transcription of its genome, a mechanism that might be important for it to maintain virulence.

Experience of meaning in life in bereaved informal caregivers of palliative care patients.

PURPOSE: Providing care for terminally ill family members places an enormous burden on informal caregivers. Meaning in life (MiL) may be a protective factor, but is jeopardised in caregiving and bereavement. This study evaluates the following questions: To what extent do bereaved informal caregivers of palliative care (PC) patients experience meaning in their lives? What differences emerge in carers compared to the general German population? How does MiL relate to well-being in former caregivers? METHODS: Eighty-four bereaved PC caregivers completed the Schedule for Meaning in Life Evaluation, the Brief Symptom Inventory, the WHOQOL-BREF, a single-item numerical rating scale of quality of life, and the Satisfaction with Life Scale. The experience of MiL of bereaved caregivers was compared to a representative population sample (n=977). RESULTS: The overall MiL fulfillment of bereaved caregivers (69 % female, age 55.5 ± 12.9 years) was significantly lower than in the general population (68.5 ± 19.2 vs. 83.3 ± 14, p<.001), as was the overall importance ascribed to their meaning framework (76.6 ± 13.6 vs. 85.6 ± 12.3, p< .001). PC caregivers are far more likely to list friends, leisure, nature/animals, and altruism. Higher MiL was correlated with better life satisfaction and quality of life. CONCLUSION: Coping with the loss of a loved one is associated with changes in MiL framework and considerably impairs a carer's experience of MiL fulfillment. Individual MiL is associated with well-being in PC caregivers during early bereavement. Specific interventions for carers targeted at meaning reconstruction during palliative care and bereavement are needed to help individuals regain a sense of meaning and purpose.

Efficient Subtractive Cloning of Genes Activated by Lipopolysaccharide and Interferon γ in Primary-Cultured Cortical Cells of Newborn Mice.

Innate immune responses play a central role in neuroprotection and neurotoxicity during inflammatory processes that are triggered by pathogen-associated molecular pattern-exhibiting agents such as bacterial lipopolysaccharide (LPS) and that are modulated by inflammatory cytokines such as interferon γ (IFNγ). Recent findings describing the unexpected complexity of mammalian genomes and transcriptomes have stimulated further identification of novel transcripts involved in specific physiological and pathological processes, such as the neural innate immune response that alters the expression of many genes. We developed a system for efficient subtractive cloning that employs both sense and antisense cRNA drivers, and coupled it with in-house cDNA microarray analysis. This system enabled effective direct cloning of differentially expressed transcripts, from a small amount (0.5 µg) of total RNA. We applied this system to isolation of genes activated by LPS and IFNγ in primary-cultured cortical cells that were derived from newborn mice, to investigate the mechanisms involved in neuroprotection and neurotoxicity in maternal/perinatal infections that cause various brain injuries including periventricular leukomalacia. A number of genes involved in the immune and inflammatory response were identified, showing that neonatal neuronal/glial cells are highly responsive to LPS and IFNγ. Subsequent RNA blot analysis revealed that the identified genes were activated by LPS and IFNγ in a cooperative or distinctive manner, thereby supporting the notion that these bacterial and cellular inflammatory mediators can affect the brain through direct but complicated pathways. We also identified several novel clones of apparently non-coding RNAs that potentially harbor various regulatory functions. Characterization of the presently identified genes will give insights into mechanisms and interventions not only for perinatal infection-induced brain damage, but also for many other innate immunity-related brain disorders.

Characterization of the rice PHO1 gene family reveals a key role for OsPHO1;2 in phosphate homeostasis and the evolution of a distinct clade in dicotyledons.

Phosphate homeostasis was studied in a monocotyledonous model plant through the characterization of the PHO1 gene family in rice (Oryza sativa). Bioinformatics and phylogenetic analysis showed that the rice genome has three PHO1 homologs, which cluster with the Arabidopsis (Arabidopsis thaliana) AtPHO1 and AtPHO1;H1, the only two genes known to be involved in root-to-shoot transfer of phosphate. In contrast to the Arabidopsis PHO1 gene family, all three rice PHO1 genes have a cis-natural antisense transcript located at the 5 ' end of the genes. Strand-specific quantitative reverse transcription-PCR analyses revealed distinct patterns of expression for sense and antisense transcripts for all three genes, both at the level of tissue expression and in response to nutrient stress. The most abundantly expressed gene was OsPHO1;2 in the roots, for both sense and antisense transcripts. However, while the OsPHO1;2 sense transcript was relatively stable under various nutrient deficiencies, the antisense transcript was highly induced by inorganic phosphate (Pi) deficiency. Characterization of Ospho1;1 and Ospho1;2 insertion mutants revealed that only Ospho1;2 mutants had defects in Pi homeostasis, namely strong reduction in Pi transfer from root to shoot, which was accompanied by low-shoot and high-root Pi. Our data identify OsPHO1;2 as playing a key role in the transfer of Pi from roots to shoots in rice, and indicate that this gene could be regulated by its cis-natural antisense transcripts. Furthermore, phylogenetic analysis of PHO1 homologs in monocotyledons and dicotyledons revealed the emergence of a distinct clade of PHO1 genes in dicotyledons, which include members having roles other than long-distance Pi transport.

Toward an integration of spirituality and religiousness into the psychosocial dimension of schizophrenia.

OBJECTIVE: Spirituality and religiousness have been shown to be highly prevalent among patients with schizophrenia. However, clinicians are rarely aware of the importance of religion and understand little of the value or difficulties it presents to treatment. This study aimed to assess the role of religion as a mediating variable in the process of coping with psychotic illness. METHOD: Semistructured interviews about religious coping were conducted with a sample of 115 outpatients with psychotic illness. RESULTS: For some patients, religion instilled hope, purpose, and meaning in their lives (71%), whereas for others, it induced spiritual despair (14%). Patients also reported that religion lessened (54%) or increased (10%) psychotic and general symptoms. Religion was also reported to increase social integration (28%) or social isolation (3%). It may reduce (33%) or increase (10%) the risk of suicide attempts, reduce (14%) or increase (3%) substance use, and foster adherence to (16%) or be in opposition to (15%) psychiatric treatment. CONCLUSIONS: Our results highlight the clinical significance of religion in the care of patients with schizophrenia. Religion is neither a strictly personal matter nor a strictly cultural one. Spirituality should be integrated into the psychosocial dimension of care. Our results suggest that the complexity of the relationship between religion and illness requires a highly sensitive approach to each unique story.

Light-regulated plant growth and development.

Plants are sessile and photo-autotrophic; their entire life cycle is thus strongly influenced by the ever-changing light environment. In order to sense and respond to those fluctuating conditions higher plants possess several families of photoreceptors that can monitor light from UV-B to the near infrared (far-red). The molecular nature of UV-B sensors remains unknown, red (R) and far-red (FR) light is sensed by the phytochromes (phyA-phyE in Arabidopsis) while three classes of UV-A/blue photoreceptors have been identified: cryptochromes, phototropins, and members of the Zeitlupe family (cry1, cry2, phot1, phot2, ZTL, FKF1, and LKP2 in Arabidopsis). Functional specialization within photoreceptor families gave rise to members optimized for a wide range of light intensities. Genetic and photobiological studies performed in Arabidopsis have shown that these light sensors mediate numerous adaptive responses (e.g., phototropism and shade avoidance) and developmental transitions (e.g., germination and flowering). Some physiological responses are specifically triggered by a single photoreceptor but in many cases multiple light sensors ensure a coordinated response. Recent studies also provide examples of crosstalk between the responses of Arabidopsis to different external factors, in particular among light, temperature, and pathogens. Although the different photoreceptors are unrelated in structure, in many cases they trigger similar signaling mechanisms including light-regulated protein-protein interactions or light-regulated stability of several transcription factors. The breath and complexity of this topic forced us to concentrate on specific aspects of photomorphogenesis and we point the readers to recent reviews for some aspects of light-mediated signaling (e.g., transition to flowering).

Peroxisome proliferator activated receptors: transcriptional regulators of adipogenesis, lipid metabolism and more....

The recent discovery of lipid-activatable transcription factors that regulate the genes controlling lipid metabolism and adipogenesis has provided insight into the way that organisms sense and respond to lipid levels. Identification of the signaling pathways in which these receptors are involved will help us to understand the control of energy balance and the molecular defects underlying its disorders.

La "bientraitance", exploration du concept et essai d'utilisation en santé publique: une expérience à Fribourg (Suisse). ["Bientraitance": conceptual exploration and an example of its application in public health: an experience from Fribourg, Switzerland]

Since the year 2000, the concept of "bientraitance" (for which no equivalent term has yet emerged in either the English or German language) has gained widespread credence among educators, sociologists and health professionals in France and Belgium. This concept emphasizes a constructive approach to care and education rather than merely one of prevention of disasters. Applied in public health, and in particular to mental health promotion, the use of the concept of "bientraitance" can help promote both effectiveness and meaning in the design and planning of community interventions. The article presents an example of an intervention for children and adolescents in Fribourg, Switzerland. The underpinning hypothesis is that the children and youth groups (such as sports clubs, artistic and cultural associations, scouts and guides) represent largely untapped, or under-tapped, informal health resources with a favourable cost-effectiveness profile. "Bientraitance" criteria are used in selecting certain associations offering structured extracurricular group educational activities and collective out-of-school (or after school) programmes. Support is provided to the organisations selected for recruiting new members, in particular those with potentially lower levels of access, for example disabled children or new migrants. The results will be evaluated for the impact of participation in various out-of-school activities on health and health determinants from a prospective and comparative perspective. This paper shows how the concept of "bientraitance" can be useful in the development of a public health intervention.

A quorum sensing regulated small volatile molecule reduces acute virulence and promotes chronic infection phenotypes.

A significant number of environmental microorganisms can cause serious, even fatal, acute and chronic infections in humans. The severity and outcome of each type of infection depends on the expression of specific bacterial phenotypes controlled by complex regulatory networks that sense and respond to the host environment. Although bacterial signals that contribute to a successful acute infection have been identified in a number of pathogens, the signals that mediate the onset and establishment of chronic infections have yet to be discovered. We identified a volatile, low molecular weight molecule, 2-amino acetophenone (2-AA), produced by the opportunistic human pathogen Pseudomonas aeruginosa that reduces bacterial virulence in vivo in flies and in an acute mouse infection model. 2-AA modulates the activity of the virulence regulator MvfR (multiple virulence factor regulator) via a negative feedback loop and it promotes the emergence of P. aeruginosa phenotypes that likely promote chronic lung infections, including accumulation of lasR mutants, long-term survival at stationary phase, and persistence in a Drosophila infection model. We report for the first time the existence of a quorum sensing (QS) regulated volatile molecule that induces bistability phenotype by stochastically silencing acute virulence functions in P. aeruginosa. We propose that 2-AA mediates changes in a subpopulation of cells that facilitate the exploitation of dynamic host environments and promote gene expression changes that favor chronic infections.

Membrane lipid composition affects plant heat sensing and modulates Ca ( 2+) -dependent heat shock response.

Understanding how plants sense and respond to heat stress is central to improve crop tolerance and productivity. Recent findings in Physcomitrella patensdemonstrated that the controlled passage of calcium ions across the plasma membrane regulates the heat shock response (HSR). To investigate the effect of membrane lipid composition on the plant HSR, we acclimated P. patens to a slightly elevated yet physiological growth temperature and analysed the signature of calcium influx under a mild heat shock. Compared to tissues grown at 22°C, tissues grown at 32°C had significantly higher overall membrane lipid saturation level and, when submitted to a short heat shock at 35°C, displayed a noticeably reduced calcium influx and a consequent reduced heat shock gene expression. These results show that temperature differences, rather than the absolute temperature, determine the extent of the plant HSR and indicate that membrane lipid composition regulates the calcium-dependent heat-signaling pathway.

Acting, predicting and intervening in a socio-hydrological world

This paper asks a simple question: if humans and their actions co-evolve with hydrological systems (Sivapalan et al., 2012), what is the role of hydrological scientists, who are also humans, within this system? To put it more directly, as traditionally there is a supposed separation of scientists and society, can we maintain this separation as socio-hydrologists studying a socio-hydrological world? This paper argues that we cannot, using four linked sections. The first section draws directly upon the concern of science-technology studies to make a case to the (socio-hydrological) community that we need to be sensitive to constructivist accounts of science in general and socio-hydrology in particular. I review three positions taken by such accounts and apply them to hydrological science, supported with specific examples: (a) the ways in which scientific activities frame socio-hydrological research, such that at least some of the knowledge that we obtain is constructed by precisely what we do; (b) the need to attend to how socio-hydrological knowledge is used in decision-making, as evidence suggests that hydrological knowledge does not flow simply from science into policy; and (c) the observation that those who do not normally label themselves as socio-hydrologists may actually have a profound knowledge of socio-hydrology. The second section provides an empirical basis for considering these three issues by detailing the history of the practice of roughness parameterisation, using parameters like Manning's n, in hydrological and hydraulic models for flood inundation mapping. This history sustains the third section that is a more general consideration of one type of socio-hydrological practice: predictive modelling. I show that as part of a socio-hydrological analysis, hydrological prediction needs to be thought through much more carefully: not only because hydrological prediction exists to help inform decisions that are made about water management; but also because those predictions contain assumptions, the predictions are only correct in so far as those assumptions hold, and for those assumptions to hold, the socio-hydrological system (i.e. the world) has to be shaped so as to include them. Here, I add to the ``normal'' view that ideally our models should represent the world around us, to argue that for our models (and hence our predictions) to be valid, we have to make the world look like our models. Decisions over how the world is modelled may transform the world as much as they represent the world. Thus, socio-hydrological modelling has to become a socially accountable process such that the world is transformed, through the implications of modelling, in a fair and just manner. This leads into the final section of the paper where I consider how socio-hydrological research may be made more socially accountable, in a way that is both sensitive to the constructivist critique (Sect. 1), but which retains the contribution that hydrologists might make to socio-hydrological studies. This includes (1) working with conflict and controversy in hydrological science, rather than trying to eliminate them; (2) using hydrological events to avoid becoming locked into our own frames of explanation and prediction; (3) being empirical and experimental but in a socio-hydrological sense; and (4) co-producing socio-hydrological predictions. I will show how this might be done through a project that specifically developed predictive models for making interventions in river catchments to increase high river flow attenuation. Therein, I found myself becoming detached from my normal disciplinary networks and attached to the co-production of a predictive hydrological model with communities normally excluded from the practice of hydrological science.

The role of astroglia in neuroprotection.

Astrocytes are the main neural cell type responsible for the maintenance of brain homeostasis. They form highly organized anatomical domains that are interconnected into extensive networks. These features, along with the expression of a wide array of receptors, transporters, and ion channels, ideally position them to sense and dynamically modulate neuronal activity. Astrocytes cooperate with neurons on several levels, including neurotransmitter trafficking and recycling, ion homeostasis, energy metabolism, and defense against oxidative stress. The critical dependence of neurons upon their constant support confers astrocytes with intrinsic neuroprotective properties which are discussed here. Conversely, pathogenic stimuli may disturb astrocytic function, thus compromising neuronal functionality and viability. Using neuroinflammation, Alzheimer's disease, and hepatic encephalopathy as examples, we discuss how astrocytic defense mechanisms may be overwhelmed in pathological conditions, contributing to disease progression.