A novel targeted/untargeted GC-Orbitrap metabolomics methodology applied to Candida albicans and Staphylococcus aureus biofilms

Introduction: Combined infections from Candida albicans and Staphylococcus aureus are a leading cause of death in the developed world. Evidence suggests that Candida enhances the virulence of Staphylococcus—hyphae penetrate through tissue barriers, while S. aureus tightly associates with the hyphae to obtain entry to the host organism. Indeed, in a biofilm state, C. albicans enhances the antimicrobial resistance characteristics of S. aureus. The association of these microorganisms is also associated with significantly increased morbidity and mortality. Due to this tight association we hypothesised that metabolic effects were also in evidence. Objectives: To explore the interaction, we used a novel GC-Orbitrap-based mass spectrometer, the Q Exactive GC, which combines the high peak capacity and chromatographic resolution of gas chromatography with the sub-ppm mass accuracy of an Orbitrap system. This allows the capability to leverage the widely available electron ionisation libraries for untargeted applications, along with expanding accurate mass libraries and targeted matches based around authentic standards. Methods: Optimised C. albicans and S. aureus mono- and co-cultured biofilms were analysed using the new instrument in addition to the fresh and spent bacterial growth media. Results: The targeted analysis experiment was based around 36 sugars and sugar phosphates, 22 amino acids and five organic acids. Untargeted analysis resulted in the detection of 465 features from fresh and spent medium and 405 from biofilm samples. Three significantly changing compounds that matched to high scoring library fragment patterns were chosen for validation. Conclusion: Evaluation of the results demonstrates that the Q Exactive GC is suitable for metabolomics analysis using a targeted/untargeted methodology. Many of the results were as expected: e.g. rapid consumption of glucose and fructose from the medium regardless of the cell type. Modulation of sugar-phosphate levels also suggest that the pentose phosphate pathway could be enhanced in the cells from co-cultured biofilms. Untargeted metabolomics results suggested significant production of cell-wall biosynthesis components and the consumption of non-proteinaceous amino-acids

Fatal miliary Coccidioidomycosis in a patient receiving infliximab therapy: a case report

A 78-year-old white male from Iowa in the United States of America receiving the anti- tumor necrois factor (TNF) agent infliximab therapy for rheumatoid arthritis developed a cheek ulcer which failed to respond to empiric antibiotic therapy. He subsequently presented with progressive respiratory failure from miliary coccidioidomycosis which proved fatal. The patient vacationed in Arizona 6 months previously and likely contracted the organism there as Iowa is not an endemic area for coccidioidomycosis. Respiratory failure from miliary infiltration is an uncommon presentation of coccidioidomycosis. Physicians should be aware of the importance of travel history and potential for life-threatening coccidioidomycosis in patients receiving tumor necrosis factor inhibitors

Dynamics of trimming the content of face representations for categorization in the brain

To understand visual cognition, it is imperative to determine when, how and with what information the human brain categorizes the visual input. Visual categorization consistently involves at least an early and a late stage: the occipito-temporal N170 event related potential related to stimulus encoding and the parietal P300 involved in perceptual decisions. Here we sought to understand how the brain globally transforms its representations of face categories from their early encoding to the later decision stage over the 400 ms time window encompassing the N170 and P300 brain events. We applied classification image techniques to the behavioral and electroencephalographic data of three observers who categorized seven facial expressions of emotion and report two main findings: (1) Over the 400 ms time course, processing of facial features initially spreads bilaterally across the left and right occipito-temporal regions to dynamically converge onto the centro-parietal region; (2) Concurrently, information processing gradually shifts from encoding common face features across all spatial scales (e.g. the eyes) to representing only the finer scales of the diagnostic features that are richer in useful information for behavior (e.g. the wide opened eyes in 'fear'; the detailed mouth in 'happy'). Our findings suggest that the brain refines its diagnostic representations of visual categories over the first 400 ms of processing by trimming a thorough encoding of features over the N170, to leave only the detailed information important for perceptual decisions over the P300

Implementing a public web based GIS service for feedback of surveillance data on communicable diseases in Sweden

BACKGROUND: Surveillance data allow for analysis, providing public health officials and policy-makers with a basis for long-term priorities and timely information on possible outbreaks for rapid response (data for action). In this article we describe the considerations and technology behind a newly introduced public web tool in Sweden for easy retrieval of county and national surveillance data on communicable diseases. METHODS: The web service was designed to automatically present updated surveillance statistics of some 50 statutory notifiable diseases notified to the Swedish Institute for Infectious Disease Control (SMI). The surveillance data is based on clinical notifications from the physician having treated the patient and laboratory notifications, merged into cases using a unique personal identification number issued to all Swedish residents. The web service use notification data from 1997 onwards, stored in a relational database at the SMI. RESULTS: The web service presents surveillance data to the user in various ways; tabulated data containing yearly and monthly disease data per county, age and sex distribution, interactive maps illustrating the total number of cases and the incidence per county and time period, graphs showing the total number of cases per week and graphs illustrating trends in the disease data. The system design encompasses the database (storing the data), the web server (holding the web service) and an in-the-middle computer (to ensure good security standards). CONCLUSIONS: The web service has provided the health community, the media, and the public with easy access to both timely and detailed surveillance data presented in various forms. Since it was introduced in May 2003, the system has been accessed more than 1,000,000 times, by more than 10,000 different viewers (over 12.600 unique IP-numbers)

Neural development features: Spatio-temporal development of the Caenorhabditis elegans neuronal network

The nematode Caenorhabditis elegans, with information on neural connectivity, three-dimensional position and cell linage provides a unique system for understanding the development of neural networks. Although C. elegans has been widely studied in the past, we present the first statistical study from a developmental perspective, with findings that raise interesting suggestions on the establishment of long-distance connections and network hubs. Here, we analyze the neuro-development for temporal and spatial features, using birth times of neurons and their three-dimensional positions. Comparisons of growth in C. elegans with random spatial network growth highlight two findings relevant to neural network development. First, most neurons which are linked by long-distance connections are born around the same time and early on, suggesting the possibility of early contact or interaction between connected neurons during development. Second, early-born neurons are more highly connected (tendency to form hubs) than later born neurons. This indicates that the longer time frame available to them might underlie high connectivity. Both outcomes are not observed for random connection formation. The study finds that around one-third of electrically coupled long-range connections are late forming, raising the question of what mechanisms are involved in ensuring their accuracy, particularly in light of the extremely invariant connectivity observed in C. elegans. In conclusion, the sequence of neural network development highlights the possibility of early contact or interaction in securing long-distance and high-degree connectivity

Determination of the Carrier-Envelope Phase of Few-Cycle Laser Pulses with Terahertz-Emission Spectroscopy

The availability of few-cycle optical pulses opens a window to physical phenomena occurring on the attosecond time scale. In order to take full advantage of such pulses, it is crucial to measure and stabilise their carrier-envelope (CE) phase, i.e., the phase difference between the carrier wave and the envelope function. We introduce a novel approach to determine the CE phase by down-conversion of the laser light to the terahertz (THz) frequency range via plasma generation in ambient air, an isotropic medium where optical rectification (down-conversion) in the forward direction is only possible if the inversion symmetry is broken by electrical or optical means. We show that few-cycle pulses directly produce a spatial charge asymmetry in the plasma. The asymmetry, associated with THz emission, depends on the CE phase, which allows for a determination of the phase by measurement of the amplitude and polarity of the THz pulse

An Over-Massive Black Hole in the Compact Lenticular Galaxy NGC1277

All massive galaxies likely have supermassive black holes at their centers, and the masses of the black holes are known to correlate with properties of the host galaxy bulge component. Several explanations have been proposed for the existence of these locally-established empirical relationships; they include the non-causal, statistical process of galaxy-galaxy merging, direct feedback between the black hole and its host galaxy, or galaxy-galaxy merging and the subsequent violent relaxation and dissipation. The empirical scaling relations are thus important for distinguishing between various theoretical models of galaxy evolution, and they further form the basis for all black hole mass measurements at large distances. In particular, observations have shown that the mass of the black hole is typically 0.1% of the stellar bulge mass of the galaxy. The small galaxy NGC4486B currently has the largest published fraction of its mass in a black hole at 11%. Here we report observations of the stellar kinematics of NGC 1277, which is a compact, disky galaxy with a mass of 1.2 x 10^11 Msun. From the data, we determine that the mass of the central black hole is 1.7 x 10^10 Msun, or 59% its bulge mass. Five other compact galaxies have properties similar to NGC 1277 and therefore may also contain over-sized black holes. It is not yet known if these galaxies represent a tail of a distribution, or if disk-dominated galaxies fail to follow the normal black hole mass scaling relations.Comment: 7 pages. 6 figures. Nature. Animation at http://www.mpia.de/~bosch/blackholes.htm

Preserving the impossible: conservation of soft-sediment hominin footprint sites and strategies for three-dimensional digital data capture.

Human footprints provide some of the most publically emotive and tangible evidence of our ancestors. To the scientific community they provide evidence of stature, presence, behaviour and in the case of early hominins potential evidence with respect to the evolution of gait. While rare in the geological record the number of footprint sites has increased in recent years along with the analytical tools available for their study. Many of these sites are at risk from rapid erosion, including the Ileret footprints in northern Kenya which are second only in age to those at Laetoli (Tanzania). Unlithified, soft-sediment footprint sites such these pose a significant geoconservation challenge. In the first part of this paper conservation and preservation options are explored leading to the conclusion that to 'record and digitally rescue' provides the only viable approach. Key to such strategies is the increasing availability of three-dimensional data capture either via optical laser scanning and/or digital photogrammetry. Within the discipline there is a developing schism between those that favour one approach over the other and a requirement from geoconservationists and the scientific community for some form of objective appraisal of these alternatives is necessary. Consequently in the second part of this paper we evaluate these alternative approaches and the role they can play in a 'record and digitally rescue' conservation strategy. Using modern footprint data, digital models created via optical laser scanning are compared to those generated by state-of-the-art photogrammetry. Both methods give comparable although subtly different results. This data is evaluated alongside a review of field deployment issues to provide guidance to the community with respect to the factors which need to be considered in digital conservation of human/hominin footprints

From red to white urine: a patient's nightmare with a rather benign outcome

<p>Abstract</p> <p>Background</p> <p>Chyluria is a medical condition with presence of chyle in the urine. The disease is most prevalent in endemic regions of Africa and the Indian subcontinent where it is mostly caused by parasitic infections, particularly lymphatic filariasis due to wucheria bancrofti. Non-parasitic chyluria, however, is a very rare finding.</p> <p>Case Presentation</p> <p>We report the case of a 48 year old woman who developed a lymphorenal fistula with chyluria following ureterrenoscopy with biopsies taken for urological work-up of persistent macrohematuria. Renal biopsy confirmed the diagnosis of benign familial hematuria due to thin basement nephropathy, a condition frequently associated with episodes of macrohematuria.</p> <p>Conclusions</p> <p>This case highlights a rare case of non-parasitic chyluria as a complication of urological work-up for macrohematuria of benign nature.</p