Regulation of the Fear Network by Mediators of Stress: Norepinephrine Alters the Balance between Cortical and Subcortical Afferent Excitation of the Lateral Amygdala

Pavlovian auditory fear conditioning involves the integration of information about an acoustic conditioned stimulus (CS) and an aversive unconditioned stimulus in the lateral nucleus of the amygdala (LA). The auditory CS reaches the LA subcortically via a direct connection from the auditory thalamus and also from the auditory association cortex itself. How neural modulators, especially those activated during stress, such as norepinephrine (NE), regulate synaptic transmission and plasticity in this network is poorly understood. Here we show that NE inhibits synaptic transmission in both the subcortical and cortical input pathway but that sensory processing is biased toward the subcortical pathway. In addition binding of NE to β-adrenergic receptors further dissociates sensory processing in the LA. These findings suggest a network mechanism that shifts sensory balance toward the faster but more primitive subcortical input

Aqueous phase synthesis of copper nanoparticles : a link between heavy metal resistance and nanoparticle synthesis ability in bacterial systems

We demonstrate aqueous phase biosynthesis of phase-pure metallic copper nanoparticles (CuNPs) using a silver resistant bacterium Morganella morganii. This is particularly important considering that there has been no report that demonstrates biosynthesis and stabilization of pure copper nanoparticles in the aqueous phase. Electrochemical analysis of bacterial cells exposed to Cu2+ ions provides new insights into the mechanistic aspect of Cu2+ ion reduction within the bacterial cell and indicates a strong link between the silver and copper resistance machinery of bacteria in the context of metal ion reduction. The outcomes of this study take us a step closer towards designing rational strategies for biosynthesis of different metal nanoparticles using microorganisms.

Experimental studies of hollow flange channel beams subject to combined bending and shear actions

This paper presents the details of an experimental study of a cold-formed steel hollow flange channel beam known as LiteSteel Beam (LSB) subject to combined bending and shear actions. The LSB sections are produced by a patented manufacturing process involving simultaneous cold-forming and electric resistance welding. Due to the geometry of the LSB, as well as its unique residual stress characteristics and initial geometric imperfections resultant of manufacturing processes, much of the existing research for common cold-formed steel sections is not directly applicable to LSB. Experimental and numerical studies have been carried out to evaluate the behaviour and design of LSBs subject to pure bending actions and predominant shear actions. To date, however, no investigation has been conducted into the strength of LSB sections under combined bending and shear actions. Combined bending and shear is especially prevalent at the supports of continuous span and cantilever beams, where the interaction of high shear force and bending moment can reduce the capacity of a section to well below that for the same section subject only to pure shear or moment. Hence experimental studies were conducted to assess the combined bending and shear behaviour and strengths of LSBs. Eighteen tests were conducted and the results were compared with current AS/NZS 4600 and AS 4100 design rules. AS/NZS 4600 design rules were shown to grossly underestimate the combined bending and shear capacities of LSBs and hence two lower bound design equations were proposed based on experimental results. Use of these equations will significantly improve the confidence and cost-effectiveness of designing LSBs for combined bending and shear actions.

The safety profile of perflutren microsphere contrast echocardiography during rest and stress imaging : results from an Australian multicentre cohort

Background Contrast enhanced echocardiography (CEE) is utilised when sub-optimal image quality results in non-diagnostic echocardiograms. However, there have been numerous safety notices issued by regulatory authorities regarding rare but potentially serious adverse reactions (AR). This multi-centre, retrospective analysis was performed to assess the short-term safety of CEE in a broad range of indications. Methods All CEE performed over 58 months at three institutions were assessed for AR within 30 min. Results A total of 5956 CEE were performed in 5576 patients. A total of 4903 were stress CEE and 1053 resting CCE.Bolus administration in 5719, infusion in 237 cases; 89.9% of CCE were outpatients. Commonest CEE indication was functional stress testing (82.3%). There were 16 AR related to CEE (0.27%). All AR were mild, transient and all patients made a full recovery. No cases of serious anaphylaxis or death within 30 min of contrast administration. Comparing those with and without an AR, there were no significant differences in age, gender, BMI, LVEF, patient location, exam type or RVSP. There was a slightly increased likelihood of an AR during infusion versus bolus dosing (p = 0.02). Conclusion CEE is a safe investigation in a broad range of indications and clinical scenarios. AR are very rare, mild and transient.

Oxidative stress induced lung cancer and COPD : opportunities for epigenetic therapy

Reactive oxygen species (ROS) form as a natural by-product of the normal metabolism of oxygen and play important roles within the cell. Under normal circumstances the cell is able to maintain an adequate homeostasis between the formation of ROS and its removal through particular enzymatic pathways or via antioxidants. If however, this balance is disturbed a situation called oxidative stress occurs. Critically, oxidative stress plays important roles in the pathogenesis of many diseases, including cancer. Epigenetics is a process where gene expression is regulated by heritable mechanisms that do not cause any direct changes to the DNA sequence itself, and disruption of epigenetic mechanisms has important implications in disease. Evidence is emerging that histone deacetylases (HDACs) play decisive roles in regulating important cellular oxidative stress pathways including those involved with sensing oxidative stress and those involved with regulating the cellular response to oxidative stress. In particular aberrant regulation of these pathways by HDACs may play critical roles in cancer progression. In this review we discuss the current evidence linking epigenetics and oxidative stress and cancer, using chronic obstructive pulmonary disease and non-small cell lung cancer to illustrate the importance of epigenetics on these pathways within these disease settings. © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Targeting oxidative stress in cancer

Importance of the field: Reactive oxygen species (ROS) occur as natural by-products of oxygen metabolism and have important cellular functions. Normally, the cell is able to maintain an adequate balance between the formation and removal of ROS either via anti-oxidants or through the use specific enzymatic pathways. However, if this balance is disturbed, oxidative stress may occur in the cell, a situation linked to the pathogenesis of many diseases, including cancer. Areas covered in this review: HDACs are important regulators of many oxidative stress pathways including those involved with both sensing and coordinating the cellular response to oxidative stress. In particular aberrant regulation of these pathways by histone deacetylases may play critical roles in cancer progression. What the reader will gain: In this review we discuss the notion that targeting HDACs may be a useful therapeutic avenue in the treatment of oxidative stress in cancer, using chronic obstructive pulmonary disease (COPD), NSCLC and hepatocellular carcinoma (HCC) as examples to illustrate this possibility. Take home message: Epigenetic mechanisms may be an important new therapeutic avenue for targeting oxidative stress in cancer. © 2010 Informa UK, Ltd.

Parents’ perception about children’s academic stress and child care related issues

The present study intends to understand the parents' perception about children's academic stress and child care related issues. A group of 139 parents, 68 fathers and 71 mothers, participated in the study voluntarily and they were selected following convenience sampling technique. In order to achieve the objective of the study, a specially designed semi-structured questionnaire was used. Findings disclosed that about one-third of the fathers (29.4%) and one-tenth of the mothers (9.9%) frankly admitted that they could not provide quality care and guidance to their children and in this regard significant difference was observed between fathers and mothers (p<.05). More than four-fifth of the parents stated that they should be friendly with their children so that children feel comfortable to share their personal issues with them. More than one-fifth fathers (27.9%) and one-fourth mothers (16.9%) applied corporal punishment as they believed it is necessary to discipline them and/or for better academic performance.

Students' academic stress and welfare as perceived by the teachers

The objective of the present study was to understand the teachers' perception about students' academic stress and other welfare related issues. A group of 125 secondary and higher secondary school teachers (43 male and 82 female) from five schools located in Kolkata were covered in the study following convenience sampling technique. Data were collected by using a semi-structured questionnaire developed by the first author. Findings revealed that more than half of the teachers (55.8% male and 54.9% female) felt that today's students are not brought up in child friendly environment while an overwhelming number of teachers stated that students face some social problems (88.4% male and 96.3% female) which affects their mental health and causes stress (90.7% male and 92.7% female). However, majority of them (79.1% male and 78% female teachers), irrespective of gender, denied the fact that teaching method followed in schools could cause academic stress. Vast majority of the teachers felt that New Education System in India i.e., making Grade X examination (popularly known as secondary examination) optional will not be beneficial for students. So far as motivation of the students is concerned, introducing innovative teaching methods like project work, field visit, using audio-visual aids in the schools has been suggested by more than 95% of the teachers. This apart, most of the teachers suggested reward system in the schools in addition to taking classes seriously by the teachers and punctuality. Reduction of load of home work was also suggested by more than two-fifth teachers. Although corporal punishment has gone down, it is still practiced by some of the teachers' especially male teachers in Kolkata. Male and female teachers differed significantly with respect to two issues only (p < .05) i.e., applying corporal punishment and impact of sexual health education. Male teachers apply more corporal punishment compared to female teachers and secondly, male teachers do not forsee any negative influence of sexual health education.

Acknowledging, moving toward and transcending psychophysiological angst during a paradox of conflicting desires

In this paper I integrate the work of a number of philosophers to clarify some psychological issues that can arise in human existence when a conflict of intrapersonal or interpersonal desires arises. This paper utilises the work of Deleuze, Freud, Jung, Heidegger, Hegel and Nietzsche to provide a conceptual framework as to how mental disturbances can arise if unconscious desires cannot be satisfied due to the experience of a resistance from a conflicting or opposing desire. This paper argues that the phenomenal experience of a conflict of desires can be unconcealed in moments of un-readiness-to-hand and from the awareness of the psychophysiological experience of stress or angst. The work that is presented, results in the conclusion that it is fundamentally necessary to embrace Nietzsche’s idea of the ‘will to power’ to overcome these difficulties and to achieve personal individuation and authentic wellbeing. This advice is in contrast to an inauthentic choice of depending on the use of Freudian defence mechanisms to conceal a conflict of desires from consciousness. A detailed theoretical example of the process involved in the resolution of a conflict of desires through self-transcendence is specifically informed by the ideas of Nietzsche and Jung.

Predicting crack initiation due to ratchetting in rail heads using critical element analysis

This paper presents a strategy to predict the lifetime of rails subjected to large rolling contact loads that induce ratchetting strains in the rail head. A critical element concept is used to calculate the number of loading cycles needed for crack initiation to occur in the rail head surface. In this technique the finite element method (FEM) is used to determine the maximum equivalent ratchetting strain per load cycle, which is calculated by combining longitudinal and shear stains in the critical element. This technique builds on a previously developed critical plane concept that has been used to calculate the number of cycles to crack initiation in rolling contact fatigue under ratchetting failure conditions. The critical element concept simplifies the analytical difficulties of critical plane analysis. Finite element analysis (FEA) is used to identify the critical element in the mesh, and then the strain values of the critical element are used to calculate the ratchetting rate analytically. Finally, a ratchetting criterion is used to calculate the number of cycles to crack initiation from the ratchetting rate calculated.

The role of epigenetics in resistance to cisplatin chemotherapy in lung cancer

Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20-30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Computer-assisted measurements of coronal knee joint laxity in vitro are related to low-stress behavior rather than structural properties of the collateral ligaments

The relationship between coronal knee laxity and the restraining properties of the collateral ligaments remains unknown. This study investigated correlations between the structural properties of the collateral ligaments and stress angles used in computer-assisted total knee arthroplasty (TKA), measured with an optically based navigation system. Ten fresh-frozen cadaveric knees (mean age: 81 ± 11 years) were dissected to leave the menisci, cruciate ligaments, posterior joint capsule and collateral ligaments. The resected femur and tibia were rigidly secured within a test system which permitted kinematic registration of the knee using a commercially available image-free navigation system. Frontal plane knee alignment and varus-valgus stress angles were acquired. The force applied during varus-valgus testing was quantified. Medial and lateral bone-collateral ligament-bone specimens were then prepared, mounted within a uni-axial materials testing machine, and extended to failure. Force and displacement data were used to calculate the principal structural properties of the ligaments. The mean varus laxity was 4 ± 1° and the mean valgus laxity was 4 ± 2°. The corresponding mean manual force applied was 10 ± 3 N and 11 ± 4 N, respectively. While measures of knee laxity were independent of the ultimate tensile strength and stiffness of the collateral ligaments, there was a significant correlation between the force applied during stress testing and the instantaneous stiffness of the medial (r = 0.91, p = 0.001) and lateral (r = 0.68, p = 0.04) collateral ligaments. These findings suggest that clinicians may perceive a rate of change of ligament stiffness as the end-point during assessment of collateral knee laxity.

Resistance is feral : digital culture, community arts, and the new cultural gatekeepers

The Community Arts sector in Australia has a history of resistance. It has challenged hegemonic culture through facilitating grassroots creative production, contesting notions of artistic processes, and the role of the artist in society. This paper examines this penchant for resistance through the lens of contemporary digital culture, to establish that the sector is continuing to challenge dominant forms of cultural control. It then proposes that this enthusiasm and activity lacks ethical direction, describing it as feral to encompass the potential of current practices, while highlighting how a level of taming is needed in order to develop ethical approaches.

An extracellular signal-regulated kinase 2 survival pathway mediates resistance of human mesothelioma cells to asbestos-induced injury

We hypothesized that normal human mesothelial cells acquire resistance to asbestos-induced toxicity via induction of one or more epidermal growth factor receptor (EGFR) - linked survival pathways (phosphoinositol-3-kinase/AKT/ mammalian target of rapamycin and extracellular signal - regulated kinase [ERK] 1/2) during simian virus 40 (SV40) transformation and carcinogenesis. Both isolated HKNM-2 mesothelial cells and a telomerase-immortalized mesothelial line (LP9/TERT-1) were more sensitive to crocidolite asbestos toxicity than an SV40 Tag-immortalized mesothelial line (MET5A) and malignant mesothelioma cell lines (HMESO and PPM Mill). Whereas increases in phosphorylation of AKT (pAKT) were observed in MET5A cells in response to asbestos, LP9/TERT-1 cells exhibited dose-related decreases in pAKT levels. Pretreatment with an EGFR phosphorylation or mitogen-activated protein kinase kinase 1/2 inhibitor abrogated asbestos-induced phosphorylated ERK (pERK) 1/2 levels in both LP9/TERT-1 and MET5A cells as well as increases in pAKT levels in MET5A cells. Transient transfection of small interfering RNAs targeting ERK1, ERK2, or AKT revealed that ERK1/2 pathways were involved in cell death by asbestos in both cell lines. Asbestos-resistant HMESO or PPM Mill cells with high endogenous levels of ERKs or AKT did not show dose-responsive increases in pERK1/ERK1, pERK2/ERK2, or pAKT/AKT levels by asbestos. However, small hairpin ERK2 stable cell lines created from both malignant mesothelioma lines were more sensitive to asbestos toxicity than shERK1 and shControl lines, and exhibited unique, tumor-specific changes in endogenous cell death - related gene expression. Our results suggest that EGFR phosphorylation is causally linkedto pERK and pAKT activation by asbestos in normal and SV40 Tag - immortalized human mesothelial cells. They also indicate that ERK2 plays a role in modulating asbestos toxicity by regulating genes critical to cell injury and survival that are differentially expressed in human mesotheliomas.

Virus resistance and gene silencing in plants can be induced by simultaneous expression of sense and antisense RNA

Many examples of extreme virus resistance and posttranscriptional gene silencing of endogenous or reporter genes have been described in transgenic plants containing sense or antisense transgenes. In these cases of either cosuppression or antisense suppression, there appears to be induction of a surveillance system within the plant that specifically degrades both the transgene and target RNAs. We show that transforming plants with virus or reporter gene constructs that produce RNAs capable of duplex formation confer virus immunity or gene silencing on the plants. This was accomplished by using transcripts from one sense gene and one antisense gene colocated in the plant genome, a single transcript that has self-complementarity, or sense and antisense transcripts from genes brought together by crossing. A model is presented that is consistent with our data and those of other workers, describing the processes of induction and execution of posttranscriptional gene silencing.