Continuing the conversation about public health ethics: education for public health professionals in Europe

An important related question is why we should teach public health ethics. Fundamentally, we must teach public health ethics because ethical practice creates and maintains public trust and public health cannot function without public trust. To serve the public—whether through controlling an outbreak of an infectious disease, preparing for or responding to public health emergencies, or reducing the impact of non-communicable diseases—communities and individuals must trust our decisions and actions. This trust grows in large part from past successes, transparent and participatory decision making, and ethical management of the inevitable moral tensions that arise in our work.S

Effects of Multimodal Load on Spatial Monitoring as Revealed by ERPs

While the role of selective attention in filtering out irrelevant information has been extensively studied, its characteristics and neural underpinnings when multiple environmental stimuli have to be processed in parallel are much less known. Building upon a dual-task paradigm that induced spatial awareness deficits for contralesional hemispace in right hemisphere-damaged patients, we investigated the electrophysiological correlates of multimodal load during spatial monitoring in healthy participants. The position of appearance of briefly presented, lateralized targets had to be reported either in isolation (single task) or together with a concurrent task, visual or auditory, which recruited additional attentional resources (dual-task). This top-down manipulation of attentional load, without any change of the sensory stimulation, modulated the amplitude of the first positive ERP response (P1) and shifted its neural generators, with a suppression of the signal in the early visual areas during both visual and auditory dual tasks. Furthermore, later N2 contralateral components elicited by left targets were particularly influenced by the concurrent visual task and were related to increased activation of the supramarginal gyrus. These results suggest that the right hemisphere is particularly affected by load manipulations, and confirm its crucial role in subtending automatic orienting of spatial attention and in monitoring both hemispaces

Conditional Gene Expression in Mycobacterium abscessus

Mycobacterium abscessus is an emerging human pathogen responsible for lung infections, skin and soft-tissue infections and disseminated infections in immunocompromised patients. It may exist either as a smooth (S) or rough (R) morphotype, the latter being associated with increased pathogenicity in various models. Genetic tools for homologous recombination and conditional gene expression are desperately needed to allow the study of M. abscessus virulence. However, descriptions of knock-out (KO) mutants in M. abscessus are rare, with only one KO mutant from an S strain described so far. Moreover, of the three major tools developed for homologous recombination in mycobacteria, only the one based on expression of phage recombinases is working. Several conditional gene expression tools have recently been engineered for Mycobacterium tuberculosis and Mycobacterium smegmatis, but none have been tested yet in M. abscessus. Based on previous experience with genetic tools allowing homologous recombination and their failure in M. abscessus, we evaluated the potential interest of a conditional gene expression approach using a system derived from the two repressors system, TetR/PipOFF. After several steps necessary to adapt TetR/PipOFF for M. abscessus, we have shown the efficiency of this system for conditional expression of an essential mycobacterial gene, fadD32. Inhibition of fadD32 was demonstrated for both the S and R isotypes, with marginally better efficiency for the R isotype. Conditional gene expression using the dedicated TetR/PipOFF system vectors developed here is effective in S and R M. abscessus, and may constitute an interesting approach for future genetic studies in this pathogen

Cell-to-Cell Signaling Influences the Fate of Prostate Cancer Stem Cells and Their Potential to Generate More Aggressive Tumors

An increasing number of malignancies has been shown to be initiated and propelled by small subpopulations of cancer stem cells (CSC). However, whether tumor aggressiveness is driven by CSC and by what extent this property may be relevant within the tumor mass is still unsettled. To address this issue, we isolated a rare tumor cell population on the basis of its CD44+CD24− phenotype from the human androgen-independent prostate carcinoma cell line DU145 and established its CSC properties. The behavior of selected CSC was investigated with respect to the bulk DU145 cells. The injection of CSC in nude mice generated highly vascularized tumors infiltrating the adjacent tissues, showing high density of neuroendocrine cells and expressing low levels of E-cadherin and β-catenin as well as high levels of vimentin. On the contrary, when a comparable number of unsorted DU145 cells were injected the resulting tumors were less aggressive. To investigate the different features of tumors in vivo, the influence of differentiated tumor cells on CSC was examined in vitro by growing CSC in the absence or presence of conditioned medium from DU145 cells. CSC grown in permissive conditions differentiated into cell populations with features similar to those of cells held in aggressive tumors generated from CSC injection. Differently, conditioned medium induced CSC to differentiate into a cell phenotype comparable to cells of scarcely aggressive tumors originated from bulk DU145 cell injection. These findings show for the first time that CSC are able to generate differentiated cells expressing either highly or scarcely aggressive phenotype, thus influencing prostate cancer progression. The fate of CSC was determined by signals released from tumor environment. Moreover, using microarray analysis we selected some molecules which could be involved in this cell-to-cell signaling, hypothesizing their potential value for prognostic or therapeutic applications

Diagnosis and management of adhesive capsulitis

Adhesive capsulitis is a musculoskeletal condition that has a disabling capability. This review discusses the diagnosis and both operative and nonoperative management of this shoulder condition that causes significant morbidity. Issues related to medications, rehabilitation, and post surgical considerations are discussed

Pond research and management in Europe: "Small is Beautiful"

The phrase "Small is Beautiful" was first used by the talented scholar Leopold Kohr (1909 131994), but it becames more popular thanks to the essays of one of his students, the British economist E. F. Schumacher, and it was coined as a response to the socially established idea that "Big is Powerful". It could be argued that this desire for "bigness" explains why current legal frameworks and the conservation planning and management related to standing waters often overlook ponds, despite their well-known value in terms of biodiversity and socio-economic benefits (Oertli et al., 2004; Cereghino et al., 2008). Of course, this is only one of several possible explanations, but it is important to understand that such long-established ideas can have a lasting effect upon the efficiency of our conservation actions. Beyond this social perspective, the history of science can also provide some explanation as to why ponds have been undervalued for so long

Towards reconciling structure and function in the nuclear pore complex

The spatial separation between the cytoplasm and the cell nucleus necessitates the continuous exchange of macromolecular cargo across the double-membraned nuclear envelope. Being the only passageway in and out of the nucleus, the nuclear pore complex (NPC) has the principal function of regulating the high throughput of nucleocytoplasmic transport in a highly selective manner so as to maintain cellular order and function. Here, we present a retrospective review of the evidence that has led to the current understanding of both NPC structure and function. Looking towards the future, we contemplate on how various outstanding effects and nanoscopic characteristics ought to be addressed, with the goal of reconciling structure and function into a single unified picture of the NPC

Single-molecule kinetics of pore assembly by the membrane attack complex

The membrane attack complex (MAC) is a hetero-oligomeric protein assembly that kills pathogens by perforating their cell envelopes. The MAC is formed by sequential assembly of soluble complement proteins C5b, C6, C7, C8 and C9, but little is known about the rate-limiting steps in this process. Here, we use rapid atomic force microscopy (AFM) imaging to show that MAC proteins oligomerize within the membrane, unlike structurally homologous bacterial pore-forming toxins. C5b-7 interacts with the lipid bilayer prior to recruiting C8. We discover that incorporation of the first C9 is the kinetic bottleneck of MAC formation, after which rapid C9 oligomerization completes the pore. This defines the kinetic basis for MAC assembly and provides insight into how human cells are protected from bystander damage by the cell surface receptor CD59, which is offered a maximum temporal window to halt the assembly at the point of C9 insertion