Proline biosynthesis regulates proline transport in Staphylococcus aureus.

Staphylococcus aureus is metabolically diverse with the ability to rapidly adapt to a vast array of nutrient sources. This allows the pathogen to colonize a variety of niches in the host. For instance, S. aureus is the leading cause of skin and soft tissue infections, a niche that has been shown to become glucose-depleted over the course of an infection. Previous studies have shown that in niches where glucose is deficient, S. aureus utilizes peptides and free amino acids as nutrient sources. Primarily, these amino acids include glutamate and amino acids that can serve as substrates for glutamate synthesis. While arginine and histidine serve as substrates in glutamate synthesis, proline is the primary source of glutamate. Indeed, S. aureus utilizes proline as a secondary carbon source only when glucose is absent, and it can be synthesized from arginine or acquired via proline transporters from its environment. Although S. aureus encodes two putative pathways for proline biosynthesis, it has been shown that pyrroline-5-carboxylate reductase (encoded by proC) is the sole proline biosynthetic pathway in S. aureus. Studies from our laboratory have revealed that despite encoding five putative proline transporters (B7H15_03660, opuC, opuD, proP, putP), only two of the transporters, PutP and B7H15_03660 are responsible for a majority of proline transport under the laboratory conditions tested. Surprisingly, when we introduced the proC mutation into the B7H15_03660 putP double mutant, we observed proline-dependent growth, even though the primary proline transporters and proline biosynthetic pathway were knocked-out. In contrast, a transporter null ΔproC strain was unable to grow. These data suggest that inhibiting proline biosynthesis alters proline transport, and therefore one or more of the additional transporters, OpuC, OpuD, and/or ProP, are activated under these conditions. After introducing opuC, opuD, and/or proP mutations into the Δ03660 ΔputP ΔproC strain, we found that both OpuC and ProP are important for proline transport. Additionally, we observed proline-dependent growth in a proline transporter null ΔproC strain when high amounts of exogenous proline are added to the media. This growth appears to be due to an acquired mutation and will be studied more in the future. Overall these studies have revealed that proline transport is tightly linked to proline biosynthesis.https://digitalcommons.unmc.edu/surp2021/1021/thumbnail.jp

Active authentication for mobile devices utilising behaviour profiling.

With nearly 6 billion subscribers around the world, mobile devices have become an indispensable component in modern society. The majority of these devices rely upon passwords and personal identification numbers as a form of user authentication, and the weakness of these point-of-entry techniques is widely documented. Active authentication is designed to overcome this problem by utilising biometric techniques to continuously assess user identity. This paper describes a feasibility study into a behaviour profiling technique that utilises historical application usage to verify mobile users in a continuous manner. By utilising a combination of a rule-based classifier, a dynamic profiling technique and a smoothing function, the best experimental result for a users overall application usage was an equal error rate of 9.8 %. Based upon this result, the paper proceeds to propose a novel behaviour profiling framework that enables a user’s identity to be verified through their application usage in a continuous and transparent manner. In order to balance the trade-off between security and usability, the framework is designed in a modular way that will not reject user access based upon a single application activity but a number of consecutive abnormal application usages. The proposed framework is then evaluated through simulation with results of 11.45 and 4.17 % for the false rejection rate and false acceptance rate, respectively. In comparison with point-of-entry-based approaches, behaviour profiling provides a significant improvement in both the security afforded to the device and user convenience

Use of intraventricular ribbon gauze to reduce particulate emboli during aortic valve replacement

BACKGROUND: The incidence of cerebrovascular accidents following aortic valve surgery remains a devastating complication. The aim of this study was to determine the number of potential embolic material arising during aortic valve replacement and to examine the efficacy of using ribbon gauze in the left ventricle during removal of the native valve and decalcification of the aortic annulus. METHODS: Ribbon gauze was inserted into the left ventricular cavity prior to aortic valve excision in an unselected, prospectively studied series of 30 patients undergoing aortic valve replacement. A further 30 lengths of ribbon gauze were soaked in the pericardiotomy blood of the same patients and all were subjected to histological analysis. RESULTS: The median number of tissue fragments from the aortic valve replacement group was significantly higher than in the control group 5 (0–18) versus 0 (0–1) (p = 3.6 × 10(-5)). The size of tissue fragments varied between 0.1 and 9.0 mm with a mean of 0.61 ± 1.12 mm and a median of 0.2 mm. There was a significantly higher number of tissue fragments associated with patients having surgery for aortic stenosis when compared with patients who had aortic regurgitation with median of 5 (0–18) versus 0 (0–3) (p = 0.8 × 10(-3)). CONCLUSION: Significant capture of particulate debris by the intraventricular ribbon gauze suggests that the technique of left ventricular ribbon gauze insertion during aortic valve excision has merit

Addressing resistance to antibiotics in systematic reviews of antibiotic interventions

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews

BALANCING INTUITION AND RATIONALITY FOR IMPROVING INNOVATION DECISION-MAKING: THE ROLE OF DESIGN CONSULTANCIES

ABSTRACT To contain risks and increase the profitability of innovation efforts, firms frequently engage in joint innovation activities with external sources of knowledge, like design consultancies. Innovation literature has given limited consideration to the strategic role that design consultancies can play in the innovation efforts of their clients. A plausible explanation reside in the difficulty to assess and quantify the quality of their output, given the intangibility of the output itself and the difficulty of connecting a knowledge-intensive output to clients' performance indicators. By analyse the data from 7 dyadic case studies, we examine design consultancies' impact on their clients' strategic decision-making as a way of capturing their strategic role in clients' innovation efforts. We conclude that design consultancies can influence clients' strategic decisions by enhancing the two main strategic decision-making mechanisms identified by the literature -rationality and intuition. Design consultancies' impact on strategic decision-making is then transferred to some indicators of innovation performance. Early involvement in problem definition and long term relationships with clients seem t.o strengthen design professionals' influence

Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use

Utilization of the PICO framework to improve searching PubMed for clinical questions

Research articl

Development of Photonic Crystal Fiber Based Gas/ Chemical Sensors

The development of highly-sensitive and miniaturized sensors that capable of real-time analytes detection is highly desirable. Nowadays, toxic or colorless gas detection, air pollution monitoring, harmful chemical, pressure, strain, humidity, and temperature sensors based on photonic crystal fiber (PCF) are increasing rapidly due to its compact structure, fast response and efficient light controlling capabilities. The propagating light through the PCF can be controlled by varying the structural parameters and core-cladding materials, as a result, evanescent field can be enhanced significantly which is the main component of the PCF based gas/chemical sensors. The aim of this chapter is to (1) describe the principle operation of PCF based gas/ chemical sensors, (2) discuss the important PCF properties for optical sensors, (3) extensively discuss the different types of microstructured optical fiber based gas/ chemical sensors, (4) study the effects of different core-cladding shapes, and fiber background materials on sensing performance, and (5) highlight the main challenges of PCF based gas/ chemical sensors and possible solutions

The Swedish Twin Registry : establishment of a biobank and other recent developments

The Swedish Twin Registry (STR) today contains more than 194,000 twins and more than 75,000 pairs have zygosity determined by an intra-pair similarity algorithm, DNA, or by being of opposite sex. Of these, approximately 20,000, 25,000, and 30,000 pairs are monozygotic, same-sex dizygotic, and opposite-sex dizygotic pairs, respectively. Since its establishment in the late 1950s, the STR has been an important epidemiological resource for the study of genetic and environmental influences on a multitude of traits, behaviors, and diseases. Following large investments in the collection of biological specimens in the past 10 years we have now established a Swedish twin biobank with DNA from 45,000 twins and blood serum from 15,000 twins, which effectively has also transformed the registry into a powerful resource for molecular studies. We here describe the main projects within which the new collections of both biological samples as well as phenotypic measures have been collected. Coverage by year of birth, zygosity determination, ethnic heterogeneity, and influences of in vitro fertilization are also described.VetenskapsrådetNIHSSFHjärt- och LungfondenAstma- och AllergiförbundetAccepte

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular