Convection and the Extracellular Matrix Dictate Inter- and Intra-Biofilm Quorum Sensing Communication in Environmental Systems.

The mechanisms and impact of bacterial quorum sensing (QS) for the coordination of population-level behaviors are well studied under laboratory conditions. However, it is unclear how, in otherwise open environmental systems, QS signals accumulate to sufficient concentration to induce QS phenotypes, especially when quorum quenching (QQ) organisms are also present. We explore the impact of QQ activity on QS signaling in spatially organized biofilms in scenarios that mimic open systems of natural and engineered environments. Using a functionally differentiated biofilm system, we show that the extracellular matrix, local flow, and QQ interact to modulate communication. In still aqueous environments, convection facilitates signal dispersal while the matrix absorbs and relays signals to the cells. This process facilitates inter-biofilm communication even at low extracellular signal concentrations. Within the biofilm, the matrix further regulates the transport of the competing QS and QQ molecules, leading to heterogenous QS behavior. Importantly, only extracellular QQ enzymes can effectively control QS signaling, suggesting that the intracellular QQ enzymes may not have evolved to degrade environmental QS signals for competition

Nanoelectromechanical coupling in fullerene peapods probed via resonant electrical transport experiments

Fullerene peapods, that is carbon nanotubes encapsulating fullerene molecules, can offer enhanced functionality with respect to empty nanotubes. However, the present incomplete understanding of how a nanotube is affected by entrapped fullerenes is an obstacle for peapods to reach their full potential in nanoscale electronic applications. Here, we investigate the effect of C60 fullerenes on electron transport via peapod quantum dots. Compared to empty nanotubes, we find an abnormal temperature dependence of Coulomb blockade oscillations, indicating the presence of a nanoelectromechanical coupling between electronic states of the nanotube and mechanical vibrations of the fullerenes. This provides a method to detect the C60 presence and to probe the interplay between electrical and mechanical excitations in peapods, which thus emerge as a new class of nanoelectromechanical systems.Comment: 7 pages, 3 figures. Published in Nature Communications. Free online access to the published version until Sept 30th, 2010, see http://www.nature.com/ncomms/journal/v1/n4/abs/ncomms1034.htm

Isolated Cervical Dystonia: Diagnosis and Classification

This document presents a consensus on the diagnosis and classification of isolated cervical dystonia (iCD) with a review of proposed terminology. The International Parkinson and Movement Disorder Society Dystonia Study Group convened a panel of experts to review the main clinical and diagnostic issues related to iCD and to arrive at a consensus on diagnostic criteria and classification. These criteria are intended for use in clinical research, but also may be used to guide clinical practice. The benchmark is expert clinical observation and evaluation. The criteria aim to systematize the use of terminology as well as the diagnostic process, to make it reproducible across centers and applicable by expert and non-expert clinicians. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations, which are incorporated into the current criteria. Three iCD presentations are described in some detail: idiopathic (focal or segmental) iCD, genetic iCD, and acquired iCD. The relationship between iCD and isolated head tremor is also reviewed. Recognition of idiopathic iCD has two levels of certainty, definite or probable, supported by specific diagnostic criteria. Although a probable diagnosis is appropriate for clinical practice, a higher diagnostic level may be required for specific research studies. The consensus retains elements proven valuable in previous criteria and omits aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of iCD expands, these criteria will need continuous revision to accommodate new advances. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Maternal and neonatal colonisation of group B streptococcus at Muhimbili National Hospital in Dar es Salaam, Tanzania: prevalence, risk factors and antimicrobial resistance

Group B streptococcus (GBS), which asymptomatically colonises the vaginal and rectal areas of women, is the leading cause of septicemia, meningitis and pneumonia in neonates. In Tanzania no studies have been done on GBS colonisation of pregnant women and neonates. This study was conducted in Dar es Salaam, Tanzania to determine the prevalence of GBS colonisation among pregnant women, the neonatal colonisation rate and the antimicrobial susceptibility, thus providing essential information to formulate a policy for treatment and prevention regarding perinatal GBS diseases. This cross sectional study involved 300 pregnant women attending antenatal clinic and their newborns delivered at Muhimbili National Hospital (MNH) between October 2008 and March 2009. High vaginal, rectal, nasal, ear and umbilical swabs were cultured on Todd Hewitt Broth and in 5% sheep blood agar followed by identification of isolates using conventional methods and testing for their susceptibility to antimicrobial agents using the Kirby-Bauer method. GBS colonisation was confirmed in 23% of pregnant women and 8.9% of neonates. A higher proportion of GBS were isolated from the vagina (12.3%) as compared to the rectum (5%). Prolonged duration of labour (>12 hrs) was significantly shown to influence GBS colonisation in neonates P < 0.05. Other risk factors such as prolonged rupture of membrane, intrapartum fever, low birth weight and HIV infection did not correlate with GBS colonisation. All isolates were sensitive to vancomycin and ampicillin. Resistance to clindamycin, erythromycin and penicillin G was found to 17.6%, 13% and 9.4%, respectively. Our findings seem to suggest that a quarter of pregnant women attending ANC clinic at MNH and approximately 10% of their newborns are colonised with GBS. All isolates were found to be sensitive to vancomycin and ampicillin which seem to be the most effective antibiotics for the time being. However there is a need for continuous antibiotics surveillance of GBS to monitor trend of resistance. The high isolation frequency of GBS among pregnant women suggests routine antenatal screening at 35 to 37 weeks of gestation in order to provide antibiotic prophylaxis to GBS carrier

Reproducibility of in-vivo OCT measured three-dimensional human lamina cribrosa microarchitecture

Purpose: To determine the reproducibility of automated segmentation of the three-dimensional (3D) lamina cribrosa (LC) microarchitecture scanned in-vivo using optical coherence tomography (OCT). Methods: Thirty-nine eyes (8 healthy, 19 glaucoma suspects and 12 glaucoma) from 49 subjects were scanned twice using swept-source (SS-) OCT in a 3.5x3.5x3.64 mm (400x400x896 pixels) volume centered on the optic nerve head, with the focus readjusted after each scan. The LC was automatically segmented and analyzed for microarchitectural parameters, including pore diameter, pore diameter standard deviation (SD), pore aspect ratio, pore area, beam thickness, beam thickness SD, and beam thickness to pore diameter ratio. Reproducibility of the parameters was assessed by computing the imprecision of the parameters between the scans. Results: The automated segmentation demonstrated excellent reproducibility. All LC microarchitecture parameters had an imprecision of less or equal to 4.2%. There was little variability in imprecision with respect to diagnostic category, although the method tends to show higher imprecision amongst healthy subjects. Conclusion: The proposed automated segmentation of the LC demonstrated high reproducibility for 3D LC parameters. This segmentation analysis tool will be useful for in-vivo studies of the LC. © 2014 Wang et al

Detection and characterization of 3D-signature phosphorylation site motifs and their contribution towards improved phosphorylation site prediction in proteins

<p>Abstract</p> <p>Background</p> <p>Phosphorylation of proteins plays a crucial role in the regulation and activation of metabolic and signaling pathways and constitutes an important target for pharmaceutical intervention. Central to the phosphorylation process is the recognition of specific target sites by protein kinases followed by the covalent attachment of phosphate groups to the amino acids serine, threonine, or tyrosine. The experimental identification as well as computational prediction of phosphorylation sites (P-sites) has proved to be a challenging problem. Computational methods have focused primarily on extracting predictive features from the local, one-dimensional sequence information surrounding phosphorylation sites.</p> <p>Results</p> <p>We characterized the spatial context of phosphorylation sites and assessed its usability for improved phosphorylation site predictions. We identified 750 non-redundant, experimentally verified sites with three-dimensional (3D) structural information available in the protein data bank (PDB) and grouped them according to their respective kinase family. We studied the spatial distribution of amino acids around phosphorserines, phosphothreonines, and phosphotyrosines to extract signature 3D-profiles. Characteristic spatial distributions of amino acid residue types around phosphorylation sites were indeed discernable, especially when kinase-family-specific target sites were analyzed. To test the added value of using spatial information for the computational prediction of phosphorylation sites, Support Vector Machines were applied using both sequence as well as structural information. When compared to sequence-only based prediction methods, a small but consistent performance improvement was obtained when the prediction was informed by 3D-context information.</p> <p>Conclusion</p> <p>While local one-dimensional amino acid sequence information was observed to harbor most of the discriminatory power, spatial context information was identified as relevant for the recognition of kinases and their cognate target sites and can be used for an improved prediction of phosphorylation sites. A web-based service (Phos3D) implementing the developed structure-based P-site prediction method has been made available at <url>http://phos3d.mpimp-golm.mpg.de</url>.</p

Systematic Analysis of Stability Patterns in Plant Primary Metabolism

Metabolic networks are characterized by complex interactions and regulatory mechanisms between many individual components. These interactions determine whether a steady state is stable to perturbations. Structural kinetic modeling (SKM) is a framework to analyze the stability of metabolic steady states that allows the study of the system Jacobian without requiring detailed knowledge about individual rate equations. Stability criteria can be derived by generating a large number of structural kinetic models (SK-models) with randomly sampled parameter sets and evaluating the resulting Jacobian matrices. Until now, SKM experiments applied univariate tests to detect the network components with the largest influence on stability. In this work, we present an extended SKM approach relying on supervised machine learning to detect patterns of enzyme-metabolite interactions that act together in an orchestrated manner to ensure stability. We demonstrate its application on a detailed SK-model of the Calvin-Benson cycle and connected pathways. The identified stability patterns are highly complex reflecting that changes in dynamic properties depend on concerted interactions between several network components. In total, we find more patterns that reliably ensure stability than patterns ensuring instability. This shows that the design of this system is strongly targeted towards maintaining stability. We also investigate the effect of allosteric regulators revealing that the tendency to stability is significantly increased by including experimentally determined regulatory mechanisms that have not yet been integrated into existing kinetic models

Early decrements in bone density after completion of neoadjuvant chemotherapy in pediatric bone sarcoma patients

<p>Abstract</p> <p>Background</p> <p>Bone mineral density (BMD) accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients by means of dual-energy x-ray absorptiometry (DXA) after completion of neoadjuvant chemotherapy.</p> <p>Methods</p> <p>DXA measurements of the lumbar spine (L2-4), both femora and calcanei were performed perioperatively in 46 children and adolescents (mean age: 14.3 years, range: 8.6-21.5 years). Mean <it>Z</it>-scores, areal BMD (g/cm²), calculated volumetric BMD (g/cm³) and bone mineral content (BMC, g) were determined.</p> <p>Results</p> <p>Lumbar spine mean Z-score was -0.14 (95% CI: -0.46 to 0.18), areal BMD was 1.016 g/cm²(95% CI: 0.950 to 1.082) and volumetric BMD was 0.330 g/cm³(95% CI: 0.314 to 0.347) which is comparable to healthy peers. For patients with a lower extremity tumor (n = 36), the difference between the affected and non-affected femoral neck was 12.1% (95% CI: -16.3 to -7.9) in areal BMD. The reduction of BMD was more pronounced in the calcaneus with a difference between the affected and contralateral side of 21.7% (95% CI: -29.3 to -14.0) for areal BMD. Furthermore, significant correlations for femoral and calcaneal DXA measurements were found with Spearman-rho coefficients ranging from ρ = 0.55 to ρ = 0.80.</p> <p>Conclusions</p> <p>The tumor disease located in the lower extremity in combination with offloading recommendations induced diminished BMD values, indicating local osteopenia conditions. However, the results revealed no significant decrements of lumbar spine BMD in pediatric sarcoma patients after completion of neoadjuvant chemotherapy. Nevertheless, it has to be taken into account that bone tumor patients may experience BMD decrements or secondary osteoporosis in later life. Furthermore, the peripheral assessment of BMD in the calcaneus via DXA is a feasible approach to quantify bone loss in the lower extremity in bone sarcoma patients and may serve as an alternative procedure, when the established assessment of femoral BMD is not practicable due to endoprosthetic replacements.</p