5-Benzylidene-4-Oxazolidinones Are Synergistic with Antibiotics for the Treatment of Staphylococcus aureus Biofilms

The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative approaches to treatment so as to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms, and, in combination with common antibiotics, are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.     

Quantum Sensing in a Physiological‐Like Cell Niche Using Fluorescent Nanodiamonds Embedded in Electrospun Polymer Nanofibers

Fluorescent nanodiamonds (fNDs) containing nitrogen vacancy (NV) centers are promising candidates for quantum sensing in biological environments. This work describes the fabrication and implementation of electrospun poly lactic‐co‐glycolic acid (PLGA) nanofibers embedded with fNDs for optical quantum sensing in an environment, which recapitulates the nanoscale architecture and topography of the cell niche. A protocol that produces uniformly dispersed fNDs within electrospun nanofibers is demonstrated and the resulting fibers are characterized using fluorescent microscopy and scanning electron microscopy (SEM). Optically detected magnetic resonance (ODMR) and longitudinal spin relaxometry results for fNDs and embedded fNDs are compared. A new approach for fast detection of time varying magnetic fields external to the fND embedded nanofibers is demonstrated. ODMR spectra are successfully acquired from a culture of live differentiated neural stem cells functioning as a connected neural network grown on fND embedded nanofibers. This work advances the current state of the art in quantum sensing by providing a versatile sensing platform that can be tailored to produce physiological‐like cell niches to replicate biologically relevant growth environments and fast measurement protocols for the detection of co‐ordinated endogenous signals from clinically relevant populations of electrically active neuronal circuits.     

Non-equilibrium particle motion in the vicinity of a single blade

The motion of sand particles close to a single moving blade was investigated using Positron Emission Particle Tracking (PEPT) during the period in which the free bed surface profile was evolving to an equilibrium shape. The area affected by the blade was divided into active and inactive regions and these were analysed separately. The characteristic heart-shape of the active region in the plan view was determined. An approximately 10-particle-diameter wide velocity transition zone is found between the two regions. While the tracer particle is in the inactive region moving away from the blade, the time dependence of the axial displacement is well described by a logarithmic relationship. The probability of particle movement towards the centre of the blade was quantified using a “central tendency” index. The calculated central tendency shows maxima at each side of the blade. The separation of the two maxima, which indicates the width of the active region, increases with fill level but is independent of rotational speed.     

Creative conservation, landscapes and loss

Conservation practice has recently begun to be transformed by the rhetoric of creative ecology and the possibility of creating (or re-creating) desired ecological conditions. This paper explores the potential conflict between these new developments and the conservation movement's long-standing dependence on a widely-shared (and widely disseminated) sense of 'the naturalness' of habitats and landscapes, and fear of their destruction. Conservation has long been driven by fear of loss of habitat, familiar features of landscapes, and of specific places. The paper discusses the potential for creative conservation to be carried out in such a way that its potential gains can be realized without cutting off the cultural engine of concern that drives conservation forwards.     

Arterial reactivity is enhanced in genetic males taking high dose estrogens

OBJECTIVES: We sought to assess whether high dose estrogen treatment is associated with enhanced arterial reactivity in genetic males. BACKGROUND: Although estrogens have been shown to enhance arterial reactivity in women, and are thereby thought to confer cardiovascular benefit, the vascular effects of long-term estrogen therapy in genetic males is unknown. METHODS: We studied the arterial physiology of 30 genetic males--15 male to female transsexuals receiving long-term high dose estrogen therapy and 15 healthy male control subjects matched for age, smoking history and vessel size. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilation [EDD]) and after nitroglycerin (GTN), an endothelium-independent dilator. Blood pressure, cholesterol and testosterone levels were also measured in each subject. RESULTS: Total testosterone and free testosterone index levels were lower in the transsexuals compared with the control subjects (p < 0.001). In contrast, EDD was significantly higher in the transsexuals than in the control males (mean [+/-SD] 7.1 +/- 3.1% vs. 3.2 +/- 2.8%, p = 0.001), as was the GTN response (21.2 +/- 6.7% vs. 14.6 +/- 3.3%, p = 0.002). Total and high density lipoprotein cholesterol, blood pressure levels and baseline vessel size were similar in the two groups. On multivariate analysis, enhanced EDD was associated independently with estrogen therapy (p = 0.02) and with low total cholesterol (p = 0.04). An enhanced GTN response was also significantly associated with estrogen therapy (p = 0.03). CONCLUSIONS: Long-term treatment with high dose estrogens is associated with enhanced arterial reactivity in genetic males, which may be due to the effects of estrogen excess or androgen deprivation, or both.     

Data management and analysis for high-throughput DNA sequencingprojects

The rapid advances in molecular biology have begun to shift many of the bottlenecks in genome research from the laboratory to the data analysis facility. The pace at which this has occurred creates a situation in which software development always has to catch up with the flow of data. Since such large-scale processes were not anticipated, the analysis infrastructure has not been fully established. Furthermore, most systems that have been built were designed by the biologists who collected the data. More recently, computer scientists, mathematicians, and engineers have taken an interest in this problem. This has had a positive effect, since it has created a tight synergy between the informatics and the biology. Several principles affected the design of the system developed at TIGR. Each of the sample preparation, sequencing, and analysis steps had to be managed, scheduled, and tracked. This information had to be made readily available to those who needed it for carrying out their tasks. Different skill levels of the users had to be taken into account. The degree of human intervention at each step had to be evaluated and built into the design. A mixed processing environment of Macintosh and Unix platforms had to be integrated. Most importantly, the system had to save time, reduce error, and ensure uniformity of the analysis and quality of the results. In the authors' experience, the tools they have built work well because of their early decisions as to which systems to use for development. The authors settled on a robust relational database management system (Sybase) and a portable development environment (C, C++)     

Comparison of laparoscopic and minilap cholecystectomy for acute cholecystitis

The charts of all patients with acute cholecystitis undergoing either laparoscopic or minilap cholecystectomy at the Chinle Comprehensive Health Care Facility between October 1, 1991, and August 15, 1993, were retrospectively reviewed. During that period, 54 patients underwent laparoscopic cholecystectomy and 45 patients had minilap procedures. The two groups had similar mean age, sex distribution, temperature, leukocyte count, gallbladder wall thickness, and duration of preoperative symptoms. While laparoscopic cholecystectomy took an average of 16 min longer to perform than minilap cholecystectomy, patients who had laparoscopic cholecystectomy had less blood loss, reduced postoperative narcotic needs, and shorter hospital stays.