Role of Protein Kinase G in Regulating Vascular Tone in Hypoxic Ovine Cerebral Arteries

Nitric oxide (NO) and its precursors have been used clinically to induce vasorelaxation long before the specific mechanism of how this operates was understood. With the discovery in 1977 of the influence of NO on guanylate cyclase, and the subsequent elucidation of the NO pathway, the role of cyclic guanidine monophosphate (cGMP)-dependent protein kinase (PKG) has been shown to be the main mediator of NO-induced vasorelaxation. Less well understood is the behavior of this pathway in conditions of long term hypoxia (LTH). It was later shown that LTH attenuates the ability of PKG to mediate vasorelaxation. How this operates is the focus of this investigation. Here we tested the hypothesis that LTH attenuates NO-induced vasorelaxation by reducing the ability of PKG to phosphorylate its target proteins that mediate vascular relaxation and contraction. A prominent target of PKG involved with vasorelaxation is the BK channel alpha protein. To examine the influence of LTH on PKG-induced vasorelaxation, and to demonstrate the relative influence of the BK channel in these conditions, we used carotid and middle cerebral arteries from normoxic and chronically hypoxic fetal and adult sheep. These arteries were denuded of endothelium and used in concentration-response relations using 5-HT as a contractant and measured contractile force. To measure the relative influence of the BK channel in these arteries, we used the selective BK channel blocker iberiotoxin. From this we demonstrated that while hypoxia affects both BK and non-BK channel mechanisms, the influence of LTH on the BK channel is dominant in the loss of PKG-mediated vasorelaxation. We also examined whether hypoxia attenuates PKG expression and specific activity, as well as the BK channel alpha and beta proteins. Using Western blotting and enzyme kinase activity assays, we learned that LTH has a modest influence on BK channel proteins expression, and no influence on PKG expression or activity. We next examined whether LTH influences protein organization, which could potentially control PKG-mediated vasorelaxation in normoxic and hypoxic conditions. Using confocal microscopy, we learned that LTH strongly alters protein organization, and specifically the proximal association of three proteins associated with vasorelaxation, namely PKG, BK-alpha and BK-beta

Genomic Signatures of Historical Allopatry and Ecological Divergence in an Island Lizard

Geographical variation amongcontiguouspopulations is frequently attributed to ecological divergence or historical isolation followed by secondary contact.Distinguishing between these effects is key to studies of incipient speciation and could be revealed by different genomic signatures. We used RAD-seq analyses to examine morphologically divergent populations of the endemic lizard (Gallotia galloti) from the volcanic island of Tenerife. Previous analyses have suggested ecological and historical causes to explain the morphological diversity. Analyses of 276,483 single nucleotide polymorphisms (SNPs) from>20 Mbp of the genome revealed one genetically divergent population from Anaga, a region associated with divergent mtDNA lineages in other Tenerife endemics. This population also has a high number of private alleles, and its divergence can be explained by historical isolation. Bayesian outlier analyses identified a small proportion of SNPs as candidates for selection (0.04%) which were strongly differentiated between xeric andmesic habitat types. Individual testing for specific xeric–mesic selection using an alternative approach also supported ecological divergence in a similarly small proportion of SNPs. The study indicates the roles of both historical isolation and ecological divergence in shaping genomic diversity in G. galloti.However, north–southmorphological divergence appears solely associated with the latter and likely involves a relatively small proportion of the genome

Key Visual Features for Rapid Categorization of Animals in Natural Scenes

In speeded categorization tasks, decisions could be based on diagnostic target features or they may need the activation of complete representations of the object. Depending on task requirements, the priming of feature detectors through top–down expectation might lower the threshold of selective units or speed up the rate of information accumulation. In the present paper, 40 subjects performed a rapid go/no-go animal/non-animal categorization task with 400 briefly flashed natural scenes to study how performance depends on physical scene characteristics, target configuration, and the presence or absence of diagnostic animal features. Performance was evaluated both in terms of accuracy and speed and d′ curves were plotted as a function of reaction time (RT). Such d′ curves give an estimation of the processing dynamics for studied features and characteristics over the entire subject population. Global image characteristics such as color and brightness do not critically influence categorization speed, although they slightly influence accuracy. Global critical factors include the presence of a canonical animal posture and animal/background size ratio suggesting the role of coarse global form. Performance was best for both accuracy and speed, when the animal was in a typical posture and when it occupied about 20–30% of the image. The presence of diagnostic animal features was another critical factor. Performance was significantly impaired both in accuracy (drop 3.3–7.5%) and speed (median RT increase 7–16 ms) when diagnostic animal parts (eyes, mouth, and limbs) were missing. Such animal features were shown to influence performance very early when only 15–25% of the response had been produced. In agreement with other experimental and modeling studies, our results support fast diagnostic recognition of animals based on key intermediate features and priming based on the subject's expertise

Development of a viable concrete printing process

A novel Concrete Printing process has been developed, inspired and informed by advances in 3D printing, which has the potential to produce highly customised building components. Whilst still in their infancy, these technologies could create a new era of architecture that is better adapted to the environment and integrated with engineering function. This paper describes the development of a viable concrete printing process with a practical example in designing and manufacturing a concrete component (called Wonder Bench) that includes service voids and reinforcement. The challenges met and those still to be overcome particularly in the evaluation of the manufacturing tolerances of prints are also discussed

The Baby Boom and later life: is critical care fit for the future?

Populations around the world are ageing while in many developed countries the proportion of elderly patients admitted to critical care is rising. It is clear that age alone should not be used as a reason for refusing intensive care admission. Critical care in this patient group is challenging in many ways: with advancing age, several physiological changes occur which all lead to a subsequent reduction of physical performance and compensatory capacity, in many cases additionally aggravated by chronic illness. Subsequently, these age-dependent changes (with or without chronic illness) increase the risk for death, treatment costs and a prolonged length of intensive care and hospital stay. This review explores the potential of using co-morbidity and frailty to predict outcome and to help to make better decisions about critical care admission in the elderly. The authors explore the challenges of using different frailty assessment tools and offer a model for holistic approach to answer these questions

A phenomenological investigation into the psychotherapist's experience of identifying, containing and processing the patient's projective identifications

The aim of the study was to describe the therapist's lived experience of identifying, containing and processing the feelings, thoughts or fantasies evoked in him by the patient's projective identifications. A question which would elicit the experience of this phenomenon was formulated by examining case histories, and modified through the use of individual pilot studies. Fifteen experienced, psychoanalytically oriented psychotherapists were interviewed. The eight psychologically richest accounts were chosen for the study. Using the empirical phenomenological method, the four protocols that most clearly reflected the phenomenon were analysed in detail, while the remaining four were used to clarify areas of uncertainty. Projective identification is conceptualised as the process whereby the patient coerces the therapist to embody an un-appropriated aspect of his (patient's) world. The context of processing a patient's projective identification was discovered to be such that the therapist finds himself coerced to embody an incongruent, unfamiliar, confusing and inauthentic state of being which is consonant with the patient's perception of him. The discomfort of the experience leads the therapist to bring to awareness and thematise his feeling-state. He alternates between avoiding this state of being, which results in conf1ict with the patient and the therapist's own values, and appropriating it, which feels inauthentic. The therapist moves from a position of trying to understand the experience in relation to his own world, to the realisation that it is co-determined by the patient. From a position of reflective distance he re-appropriates aspects of his world that were closed to him while under the influence of the patient, in addition to appropriating previously unowned aspects. The therapist dialogues these appropriations with the invoked feelings, allowing him to differentiate those aspects of his feeling-state which are authentically his from those which are unowned aspects of the patient's aspects of his world that were closed to him while under the influence of the patient, in addition to appropriating previously unowned aspects. The therapist dialogues these appropriations with the invoked feelings, allowing him to differentiate those aspects of his feeling-state which are authentically his from those which are unowned aspects of the patient's world that he has been forced to embody. Through this process the therapist clarifies and gives meaning to his feelings. The therapist fee1s re1ieved and lighter, when in the service of the therapy, he temporarily gives himself over to the patient's experience of him, without feeling drawn to either disowning or appropriating it, while simultaneously remaining open to his own authentic reality. These findings were dialogued with the literature on projective identification

Psycho-diagnostics in a Xhosa Zionist church

A large number of Black patients seen by the mental health team in South Africa consult indigenous healers. An awareness of the diagnosis and treatment given to patients by traditional healers, would therefore enhance both the rapport with and treatment of those patients who seek help from the mental health professionals and para-professionals

A phenomenological investigation into the psychotherapist's experience of identifying, containing and processing the patient's projective identifications

The aim of the study was to describe the therapist's lived experience of identifying, containing and processing the feelings, thoughts or fantasies evoked in him by the patient's projective identifications. A question which would elicit the experience of this phenomenon was formulated by examining case histories, and modified through the use of individual pilot studies. Fifteen experienced, psychoanalytically oriented psychotherapists were interviewed. The eight psychologically richest accounts were chosen for the study. Using the empirical phenomenological method, the four protocols that most clearly reflected the phenomenon were analysed in detail, while the remaining four were used to clarify areas of uncertainty. Projective identification is conceptualised as the process whereby the patient coerces the therapist to embody an un-appropriated aspect of his (patient's) world. The context of processing a patient's projective identification was discovered to be such that the therapist finds himself coerced to embody an incongruent, unfamiliar, confusing and inauthentic state of being which is consonant with the patient's perception of him. The discomfort of the experience leads the therapist to bring to awareness and thematise his feeling-state. He alternates between avoiding this state of being, which results in conf1ict with the patient and the therapist's own values, and appropriating it, which feels inauthentic. The therapist moves from a position of trying to understand the experience in relation to his own world, to the realisation that it is co-determined by the patient. From a position of reflective distance he re-appropriates aspects of his world that were closed to him while under the influence of the patient, in addition to appropriating previously unowned aspects. The therapist dialogues these appropriations with the invoked feelings, allowing him to differentiate those aspects of his feeling-state which are authentically his from those which are unowned aspects of the patient's aspects of his world that were closed to him while under the influence of the patient, in addition to appropriating previously unowned aspects. The therapist dialogues these appropriations with the invoked feelings, allowing him to differentiate those aspects of his feeling-state which are authentically his from those which are unowned aspects of the patient's world that he has been forced to embody. Through this process the therapist clarifies and gives meaning to his feelings. The therapist fee1s re1ieved and lighter, when in the service of the therapy, he temporarily gives himself over to the patient's experience of him, without feeling drawn to either disowning or appropriating it, while simultaneously remaining open to his own authentic reality. These findings were dialogued with the literature on projective identification

Organizational learning context and firm profiles: an empirical

Which is the appropriate context to create and maintain an optimum level of organisational learning? What kind of firms have the suitable context to institutionalise its knowledge? Using data collected from 602 Spanish firms, empirical research is developed to answer these questions. As an initial step and to reply the first one, a scale for the construct organisational learning context is defined. To response the second interrogation, this paper explores the features of the firms with a favourable context to originate and keep up the capability of learning in comparison with those whose context is unfavourable. Our findings allow us to reveal the profile of the firms according with its organisational learning context