Parallel Imaging with RASER using Multiband Frequency-modulated Excitation Pulses

The many advantages of the recently proposed RASER sequence have been demonstrated. Hence, RASER holds great promises for functional MRI (fMRI), particularly for studies of the orbital-frontal cortex and other brain regions near air cavities, which cause distortion and signal loss in conventional EPI methods. However, the single-shot RASER sequence implemented so far inherently presents a set of temporal and spatial limitations that hinders it feasibility and full potential for fMRI applications. It is believed that parallel imaging will help overcome such restrictions. In this work, the RASER acquisition and reconstruction scheme is extended for parallel imaging using tailored pulses for simultaneous multi-band excitation

Regulatory Adaptation of Staphylococcus aureus during Nasal Colonization of Humans

The nasopharynx is the main ecological niche of the human pathogen Staphylococcus aureus. Although colonization of the nares is asymptomatic, nasal carriage is a known risk factor for endogenous staphylococcal infection. We quantified S. aureus mRNA levels in nose swabs of persistent carriers to gain insight into the regulatory adaptation of the bacterium to the nasal environment. We could elucidate a general response of the pathogen to the surrounding milieu independent of the strain background or the human host. Colonizing bacteria preferentially express molecules necessary for tissue adherence or immune-evasion whereas toxins are down regulated. From the analysis of regulatory loci we found evidence for a predominate role of the essential two-component system WalKR of S. aureus. The results suggest that during persistent colonization the bacteria are metabolically active with a high cell surface turnover. The increased understanding of bacterial factors that maintain the colonization state can open new therapeutic options to control nasal carriage and subsequent infections

Size reduction of complex networks preserving modularity

The ubiquity of modular structure in real-world complex networks is being the focus of attention in many trials to understand the interplay between network topology and functionality. The best approaches to the identification of modular structure are based on the optimization of a quality function known as modularity. However this optimization is a hard task provided that the computational complexity of the problem is in the NP-hard class. Here we propose an exact method for reducing the size of weighted (directed and undirected) complex networks while maintaining invariant its modularity. This size reduction allows the heuristic algorithms that optimize modularity for a better exploration of the modularity landscape. We compare the modularity obtained in several real complex-networks by using the Extremal Optimization algorithm, before and after the size reduction, showing the improvement obtained. We speculate that the proposed analytical size reduction could be extended to an exact coarse graining of the network in the scope of real-space renormalization.Comment: 14 pages, 2 figure

Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE

Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults

Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here

Characterization and Comparison of 2 Distinct Epidemic Community-Associated Methicillin-Resistant Staphylococcus aureus Clones of ST59 Lineage.

Sequence type (ST) 59 is an epidemic lineage of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal cassette mec (SCCmec) VT, and is frequently isolated from patients with severe disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a frequent colonizer of healthy children. Isolates of both clones were characterized by their ability to adhere to respiratory A549 cells, cytotoxicity to human neutrophils, and nasal colonization of a murine and murine sepsis models. Genome variation was determined by polymerase chain reaction of selected virulence factors and by multi-strain whole genome microarray. Additionally, the expression of selected factors was compared between the 2 clones. The Taiwan clone showed a much higher cytotoxicity to the human neutrophils and caused more severe septic infections with a high mortality rate in the murine model. The clones were indistinguishable in their adhesion to A549 cells and persistence of murine nasal colonization. The microarray data revealed that the Taiwan clone had lost the ø3-prophage that integrates into the β-hemolysin gene and includes staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for human immune evasion, scn and chps. Production of the virulence factors did not differ significantly in the 2 clonal groups, although more α-toxin was expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and an animal infection model. The evolutionary acquisition of PVL, the higher expression of α-toxin, and possibly the loss of a large portion of the β-hemolysin-converting prophage likely contribute to its higher pathogenic potential than the Asian-Pacific clone

Adaptive Evolution of Staphylococcus aureus during Chronic Endobronchial Infection of a Cystic Fibrosis Patient

The molecular adaptation of Staphylococcus aureus to its host during chronic infection is not well understood. Comparative genome sequencing of 3 S. aureus isolates obtained sequentially over 26 months from the airways of a cystic fibrosis patient, revealed variation in phage content, and genetic polymorphisms in genes which influence antibiotic resistance, and global regulation of virulence. The majority of polymorphisms were isolate-specific suggesting the existence of an heterogeneous infecting population that evolved from a single infecting strain of S. aureus. The genetic variation identified correlated with differences in growth rate, hemolytic activity, and antibiotic sensitivity, implying a profound effect on the ecology of S. aureus. In particular, a high frequency of mutations in loci associated with the alternate transcription factor SigB, were observed. The identification of genes under diversifying selection during long-term infection may inform the design of novel therapeutics for the control of refractory chronic infections