Formation of the Legionella-containing vacuole: phosphoinositide conversion,GTPase modulation and ER dynamics

The environmental bacterium Legionella pneumophila replicates in free-living amoeba as well as in alveolar macrophages upon inhalation of bacteria-laden aerosols. Resistance of the opportunistic pathogen to macrophages is a prerequisite to cause a severe pneumonia called Legionnaires’ disease. L. pneumophila grows intracellularly in a unique, ER-associated compartment, the Legionella-containing vacuole (LCV). The bacterial Icm/Dot type IV secretion system represents an essential virulence factor, which translocates approximately 300 “effector proteins” into protozoan or mammalian host cells. Some of these effectors contribute to the formation of the LCV by targeting conserved host factors implicated in membrane dynamics, such as phosphoinositide lipids and small GTPases. Here we review recent findings on the role of phosphoinositides, small and large GTPases as well as ER dynamics for pathogen vacuole formation and intracellular replication of L. pneumophila.     

Volubility of the human infant: Effects of parental interaction (or lack of it)

Although parental volubility, or amount of talk, has received considerable recent attention, infant volubility has received comparatively little attention despite its potential significance for communicative risk status and later linguistic and cognitive outcomes. Volubility of 16 typically developing infants from 2 to 11 months of age was longitudinally investigated in the present study across three social circumstances: parent talking to infant, parent not talking to infant and parent talking to interviewer while the infant was in the room. Results indicated that volubility was least in the Interview circumstance. There were no significant differences in volubility between the parent Talk and No Talk circumstances. Volubility was found to reduce with age. These results suggest that infants vocalise in a variety of circumstances, even when no one talks to or interacts with them. The presence of a stranger or perhaps overhearing adults speaking to each other, however, may significantly reduce infant volubility.     

Regeneration-associated macrophages：a novel approach to boost intrinsic regenerative capacity for axon regeneration

Axons in central nervous system (CNS) do not regenerate spontaneously after injuries such as stroke and traumatic spinal cord injury. Both intrinsic and extrinsic factors are responsible for the regeneration fail-ure. Although intensive research efforts have been invested on extrinsic regeneration inhibitors, the extent to which glial inhibitors contribute to the regeneration failurein vivo still remains elusive. Recent exper-imental evidence has rekindled interests in intrinsic factors for the regulation of regeneration capacity in adult mammals. In this review, we propose that activating macrophages with pro-regenerative molecular signatures could be a novel approach for boosting intrinsic regenerative capacity of CNS neurons. Using a conditioning injury model in which regeneration of central branches of dorsal root ganglia sensory neu-rons is enhanced by a preceding injury to the peripheral branches, we have demonstrated that perineuronal macrophages surrounding dorsal root ganglia neurons are critically involved in the maintenance of en-hanced regeneration capacity. Neuron-derived chemokine (C-C motif) ligand 2 (CCL2) seems to mediate neuron-macrophage interactions conveying injury signals to perineuronal macrophages taking on a soley pro-regenerative phenotype, which we designate as regeneration-associated macrophages (RAMs). Ma-nipulation of the CCL2 signaling could boost regeneration potential mimicking the conditioning injury, suggesting that the chemokine-mediated RAM activation could be utilized as a regenerative therapeutic strategy for CNS injuries.     

Brain activity and connectivity in response to negative affective stimuli: Impact of dysphoric mood and sex across diagnoses

Negative affective stimuli elicit behavioral and neural responses which vary on a continuum from adaptive to maladaptive, yet are typically investigated in a dichotomous manner (healthy controls vs. psychiatric diagnoses). This practice may limit our ability to fully capture variance from acute responses to negative affective stimuli to psychopathology at the extreme end. To address this, we conducted a functional magnetic resonance imaging study to examine the neural responses to negative valence/high arousal and neutral valence/low arousal images as a function of dysphoric mood and sex across individuals (n = 99) who represented traditional categories of healthy controls, major depressive disorder, bipolar psychosis, and schizophrenia. Observation of negative (vs. neutral) stimuli elicited blood oxygen‐level dependent responses in the following circuitry: periaqueductal gray, hypothalamus (HYPO), amygdala (AMYG), hippocampus (HIPP), orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and greater connectivity between AMYG and mPFC. Across all subjects, severity of dysphoric mood was associated with hyperactivity of HYPO, and, among females, right (R) AMYG. Females also demonstrated inverse relationships between severity of dysphoric mood and connectivity between HYPO ‐ R OFC, R AMYG ‐ R OFC, and R AMYG ‐ R HIPP. Overall, our findings demonstrated sex‐dependent deficits in response to negative affective stimuli increasing as a function of dysphoric mood state. Females demonstrated greater inability to regulate arousal as mood became more dysphoric. These findings contribute to elucidating biosignatures associated with response to negative stimuli across disorders and suggest the importance of a sex‐dependent lens in determining these biosignatures. Hum Brain Mapp 37:3733–3744, 2016. © 2016 Wiley Periodicals, Inc .     

Evolution of Visceral Sensitivity in Patients with Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) has been associated with visceral hypersensitivity. Here we examined the evolution of rectal sensitivity and of gastrointestinal symptomatology in IBS patients over time, to verify if the clinical and biological parameters showed parallel behavior. Patients complaining of IBS, identified by Rome 1 criteria, were included in this study. The severity of the gastrointestinal (Gastrointestinal) symptoms was assessed by a gastrointestinal index. The pain threshold to rectal distension was measured by a barostat programmed for phasic ascending distensions. Both measures were obtained before and after treatment. Thirty-nine patients were followed while on a 10-week group psychotherapy (psy) program. Twelve patients were controlled after pharmacological treatment with amitriptyline (Ami) 10 mg hours for two weeks and then 25 mg hours for the following 4 weeks. Clinical improvement with symptom reduction was achieved in both patients groups. With psy, the Gastrointestinal index declined from an initial value of 78.4 ± 4.8 to 65.5 ± 4.5 at the end of treatment (P < 0.05). With Ami, the gastrointestinal index decreased from 91.6 ± 5.6 to 61.8 ± 9.1 (p < 0.01). The pain threshold to rectal distension increased from 27.7 ± 1.0 to 33.7 ± 1.9 mmHg (P < 0.01) after drug treatment, but remained unchanged (30.6 ± 1.0 vs 30.6 ± 1.1 mm Hg) with psy. Evolution of the gastrointestinal index and rectal sensitivity were directly correlated (r = –0.71; P < 0.01) in Ami patients, but not in those treated with Psy (r = –0.001). In conclusion, visceral hypersensitivity appeared as a stable biological defect over a 10- to 12-week period during clinically-effective treatment with psychotherapy. Rectal pain threshold, however, seemed to be pharmacologically manipulatable in patients treated with Ami.     

The aphasic person's views of the encounter with other people: a grounded theory analysis

Being affected by aphasia influences the total life experience. The aim of this study was to generate a theoretical model, from a nursing perspective, of what aphasic persons (n = 12) experience in encounters with other people. Data were collected through interviews which adopted a biophysical, socio-cultural and psychological approach and then analysed using grounded theory method. Two main categories emerged, namely: 'interaction' and 'support'. Encountered experiences led to: 'a feeling of having ability'; 'a feeling of being an outsider'; and 'a feeling of dejection or uncertainty'. The feeling state was dependent on whether the interaction was 'obstructed' or 'secure' and on whether the support resulted in 'strengthened' or 'impaired' self-esteem. Therefore nurses need to give support that enhances patients' self-esteem and which results in them gaining a positive and realistic view of their aphasia, as well as involving those around them in this perspective. This then will give the possibility for the patient to turn the interaction process from an obstructed into a secure one.     

Nursing morale: predictive variables among a sample of registered nurses in Australia

Aim  This study investigates the determinants of morale among Registered Nurses in Queensland, Australia.
Background  In light of the public discussions on the issues facing the future of nursing, it is critical to understand the factors that influence morale.
Methods  A 160-question instrument sought information from Registered Nurses on their perceptions of 'self', work and morale. A response rate of 41% was achieved ( n  = 343) from a convenience sample of three acute hospitals.
Results  Following binary logistic regression modelling for organizational morale, significant relationships were found with patient care provision and team interaction. Binary logistic regression modelling for personal morale revealed positive relationships with team interaction, consultation, professional recognition and lower levels of patient abuse.
Conclusion  The results point to a number of organizational and professional issues that can be considered by health care administrators and policy makers to develop workplaces that have a positive impact on the morale of nurses.     

Selection of nonlinear interactions by a forward stepwise algorithm: Application to identifying environmental chemical mixtures affecting health outcomes

In this paper, we propose a stepwise forward selection algorithm for detecting the effects of a set of correlated exposures and their interactions on a health outcome of interest when the underlying relationship could potentially be nonlinear. Though the proposed method is very general, our application in this paper remains to be on analysis of multiple pollutants and their interactions. Simultaneous exposure to multiple environmental pollutants could affect human health in a multitude of complex ways. For understanding the health effects of multiple environmental exposures, it is often important to identify and estimate complex interactions among exposures. However, this issue becomes analytically challenging in the presence of potential nonlinearity in the outcome-exposure response surface and a set of correlated exposures. Through simulation studies and analyses of test datasets that were simulated as a part of a data challenge in multipollutant modeling organized by the National Institute of Environmental Health Sciences ( http://www.niehs.nih.gov/about/events/pastmtg/2015/statistical/ ), we illustrate the advantages of our proposed method in comparison with existing alternative approaches. A particular strength of our method is that it demonstrates very low false positives across empirical studies. Our method is also used to analyze a dataset that was released from the Health Outcomes and Measurement of the Environment Study as a benchmark beta-tester dataset as a part of the same workshop.     

Penalized integrative semiparametric interaction analysis for multiple genetic datasets

In this article, we consider a semiparametric additive partially linear interaction model for the integrative analysis of multiple genetic datasets. The goals are to identify important genetic predictors and gene-gene interactions and to estimate the nonparametric functions that describe the environmental effects at the same time. To find the similarities and differences of the genetic effects across different datasets, we impose a group structure on the regression coefficients matrix under the homogeneity assumption, ie, models for different datasets share the same sparsity structure, but the coefficients may differ across datasets. We develop an iterative approach to estimate the parameters of main effects, interactions and nonparametric functions, where a reparametrization of interaction parameters is implemented to meet the strong hierarchy assumption. We demonstrate the advantages of the proposed method in identification, estimation, and prediction in a series of numerical studies. We also apply the proposed method to the Skin Cutaneous Melanoma data and the lung cancer data from the Cancer Genome Atlas.