Genetic analysis of the human tumor necrosis factor alpha/cachectin promoter region in a macrophage cell line.

The 615-bp 5' flanking region of the human TNF-alpha/cachectin gene was isolated and ligated to the luciferase reporter gene. In addition, a series of truncated promoter constructs was generated by exonuclease III digestion. The promoter activity of these constructs was studied in a transient transfection system using the TNF-alpha-producing U937 cell line. Full-length and truncated TNF promoter constructions extending from -615 to -95 bp relative to the transcription start site (TSS) could be induced by phorbol esters. A construct truncated to within 36 bp of the TSS (and within 11 bp of the TATAA box) was inactive. Therefore, the phorbol ester responsive is localized in the TNF/cachectin promoter to a relatively short region proximal to the TATAA box

A viscoelastic deadly fluid in carnivorous pitcher plants

Background : The carnivorous plants of the genus Nepenthes, widely distributed in the Asian tropics, rely mostly on nutrients derived from arthropods trapped in their pitcher-shaped leaves and digested by their enzymatic fluid. The genus exhibits a great diversity of prey and pitcher forms and its mechanism of trapping has long intrigued scientists. The slippery inner surfaces of the pitchers, which can be waxy or highly wettable, have so far been considered as the key trapping devices. However, the occurrence of species lacking such epidermal specializations but still effective at trapping insects suggests the possible implication of other mechanisms. Methodology/Principal Findings : Using a combination of insect bioassays, high-speed video and rheological measurements, we show that the digestive fluid of Nepenthes rafflesiana is highly viscoelastic and that this physical property is crucial for the retention of insects in its traps. Trapping efficiency is shown to remain strong even when the fluid is highly diluted by water, as long as the elastic relaxation time of the fluid is higher than the typical time scale of insect movements. Conclusions/Significance : This finding challenges the common classification of Nepenthes pitchers as simple passive traps and is of great adaptive significance for these tropical plants, which are often submitted to high rainfalls and variations in fluid concentration. The viscoelastic trap constitutes a cryptic but potentially widespread adaptation of Nepenthes species and could be a homologous trait shared through common ancestry with the sundew (Drosera) flypaper plants. Such large production of a highly viscoelastic biopolymer fluid in permanent pools is nevertheless unique in the plant kingdom and suggests novel applications for pest control

Semantic diversity:A measure of contextual variation in word meaning based on latent semantic analysis

Semantic ambiguity is typically measured by summing the number of senses or dictionary definitions that a word has. Such measures are somewhat subjective and may not adequately capture the full extent of variation in word meaning, particularly for polysemous words that can be used in many different ways, with subtle shifts in meaning. Here, we describe an alternative, computationally derived measure of ambiguity based on the proposal that the meanings of words vary continuously as a function of their contexts. On this view, words that appear in a wide range of contexts on diverse topics are more variable in meaning than those that appear in a restricted set of similar contexts. To quantify this variation, we performed latent semantic analysis on a large text corpus to estimate the semantic similarities of different linguistic contexts. From these estimates, we calculated the degree to which the different contexts associated with a given word vary in their meanings. We term this quantity a word's semantic diversity (SemD). We suggest that this approach provides an objective way of quantifying the subtle, context-dependent variations in word meaning that are often present in language. We demonstrate that SemD is correlated with other measures of ambiguity and contextual variability, as well as with frequency and imageability. We also show that SemD is a strong predictor of performance in semantic judgments in healthy individuals and in patients with semantic deficits, accounting for unique variance beyond that of other predictors. SemD values for over 30,000 English words are provided as supplementary materials. © 2012 Psychonomic Society, Inc

Cyanobacterial bloom mitigation using proteins with high isoelectric point and chitosan-modified soil

A new environmental friendly method was developed for cyanobacterial blooms mitigation using local lake shore soil modified by protein with high isoelectric point (pI) and chitosan jointly. Results suggested that 5 mg/L lysozyme (pI ≈ 11) and 100 mg/L bromelain (pI ≈ 9.5) modified 10 mg/L soil can both reduce the surface charge of microcystis aeruginosa, the dominant species forming cyanobacterial blooms, from -26 mv to -10 mv and remove 73% and 60% of algal cells in 30 min, respectively. The limited improvement of removal efficiency was due to the small flocs (< 60 μm) formed by charge neutralization, which need more than 90 min to settle in static condition. However, when the small flocs were linked and bridged by the other modifier, chitosan with long polymer chain, large flocs of about 800 μm and 300 μm were fomed and more than 80% of algal cells were removed in 5 min and 30 min by lysozyme-chitosan modified soil and bromelain-chitosan modified soil, respectively. The lower removal ability of bromelain-modified soil was due to the lower charge density leading to less powerful in destabilization of algal cells. Depending on the bi-component modification mechanism including charge neutralization of proteins with high pI and netting and bridging function of chitosan with long polymer chain, it is possible to flocculate cyanobacterial blooms in natural waters effectively using locally available materials

Turbulent ‘stopping plumes’ and plume pinch-off in uniform surroundings

Observations of turbulent convection in the environment are of variously sus- tained plume-like flows or intermittent thermal-like flows. At different times of the day the prevailing conditions may change and consequently the observed flow regimes may change. Understanding the link between these flows is of practical importance meteorologically, and here we focus our interest upon plume-like regimes that break up to form thermal-like regimes. It has been shown that when a plume rises from a boundary with low conductivity, such as arable land, the inability to maintain a rapid enough supply of buoyancy to the plume source can result in the turbulent base of the plume separating and rising away from the source. This plume ‘pinch-off’ marks the onset of the intermittent thermal-like behavior. The dynamics of turbulent plumes in a uniform environment are explored in order to investigate the phenomenon of plume pinch-off. The special case of a turbulent plume having its source completely removed, a ‘stopping plume’, is considered in particular. The effects of forcing a plume to pinch-off, by rapidly reducing the source buoyancy flux to zero, are shown experi- mentally. We release saline solution into a tank filled with fresh water generating downward propagating steady turbulent plumes. By rapidly closing the plume nozzle, the plumes are forced to pinch-off. The plumes are then observed to detach from the source and descend into the ambient. The unsteady buoyant region produced after pinch-off, cannot be described by the power-law behavior of either classical plumes or thermals, and so the terminology ‘stopping plume’ (analogous to a ‘starting plume’) is adopted for this type of flow. The propagation of the stopping plume is shown to be approximately linearly dependent on time, and we speculate therefore that the closure of the nozzle introduces some vorticity into the ambient, that may roll up to form a vortex ring dominating the dynamics of the base of a stopping plume

Evaluating Retinal Function in Age-Related Maculopathy with the ERG Photostress Test

PURPOSE. To evaluate the diagnostic potential of the electroretinogram (ERG) photostress test and the focal cone ERG in age-related maculopathy (ARM). METHODS. The cohort comprised 31 patients with ARM and 27 age-matched control subjects. The ERG photostress test was used to monitor cone adaptation after intense light adaptation. Focal 41- and 5-Hz cone ERGs were recorded monocularly (central 20°) to assess steady state retinal function. Univariate analysis identified electrophysiological parameters that differed between groups, and receiver operating characteristic (ROC) curves were constructed to assess their diagnostic potential. Logistic regression analysis determined the diagnostic potential of a model incorporating several independent predictors of ARM. RESULTS. The rate of recovery of the ERG photostress test was reduced (recovery was slower) in subjects with ARM. The parameter exhibited good diagnostic potential (P = 0.002, area under ROC curve = 0.74). The implicit times of the 5-Hz (a-wave, P = 0.002; b-wave, P < 0.001) and the 41-Hz (P < 0.001) focal cone ERGs were increased, and the 41-Hz focal cone ERG amplitude (P = 0.003) and focal to full-field amplitude ratio (P = 0.001) were reduced in the ARM group. Logistic regression analysis identified three independent predictors of ARM, including the rate of recovery of the ERG photostress test. CONCLUSIONS. Early ARM has a marked effect on the kinetics of cone adaptation. The clinical application of the ERG photostress test increases the sensitivity and specificity of a model for the diagnosis of ARM. Improved assessment of the functional integrity of the central retina will facilitate early diagnosis and evaluation of therapeutic interventions

Automated operant assessments of Huntington's Disease mouse models

Huntington’s disease (HD) presents clinically with a triad of motor, cognitive, and psychiatric symptoms. Cognitive symptoms often occur early within the disease progression, prior to the onset of motor symptoms, and they are significantly burdensome to people who are affected by HD. In order to determine the suitability of mouse models of HD in recapitulating the human condition, these models must be behaviorally tested and characterized. Operant behavioral testing offers an automated and objective method of behaviorally profiling motor, cognitive, and psychiatric dysfunction in HD mice. Furthermore, operant testing can also be employed to determine any behavioral changes observed after any associated interventions or experimental therapeutics. We here present an overview of the most commonly used operant behavioral tests to dissociate motor, cognitive, and psychiatric aspects of mouse models of HD

Use of Motor Abundance in Young and Older Adults during Dual-Task Treadmill Walking

Contains fulltext : 110120.pdf (publisher's version ) (Open Access)Motor abundance allows individuals to perform any task reliably while being variable in movement's particulars. The study investigated age-related differences in this feature when young adults (YA) and older adults (OA) performed challenging tasks, namely treadmill walking alone and while performing a cognitive task. A goal function for treadmill walking was first defined, i.e., maintain constant speed at each step, which led to a goal equivalent manifold (GEM) containing all combinations of step time and step length that equally satisfied the function. Given the GEM, amounts of goal-equivalent and non-goal-equivalent variability were afterwards determined and used to define an index providing information about the set of effective motor solutions relative to the GEM. The set was limited in OA compared to YA in treadmill walking alone, indicating that OA made less flexible use of motor abundance than YA. However, this differentiation between YA and OA disappeared when concurrently performing the cognitive task. It is proposed that OA might have benefited from cognitive compensation

Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection

Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001) and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB), induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with cardiac dysfunction in clinical and experimental sepsis and ultimately resulted in depressed cardiomyocyte contractile performance along with rhythm disturbance. Our study proposes a detailed molecular mechanism of pneumococcal toxin-induced cardiac injury and highlights the major translational potential of targeting circulating PLY to protect against cardiac complications during pneumococcal infections

Developing an agenda for research about policies to improve access to healthy foods in rural communities: a concept mapping study

Background Policies that improve access to healthy, affordable foods may improve population health and reduce health disparities. In the United States most food access policy research focuses on urban communities even though residents of rural communities face disproportionately higher risk for nutrition-related chronic diseases compared to residents of urban communities. The purpose of this study was to (1) identify the factors associated with access to healthy, affordable food in rural communities in the United States; and (2) prioritize a meaningful and feasible rural food policy research agenda. Methods This study was conducted by the Rural Food Access Workgroup (RFAWG), a workgroup facilitated by the Nutrition and Obesity Policy Research and Evaluation Network. A national sample of academic and non-academic researchers, public health and cooperative extension practitioners, and other experts who focus on rural food access and economic development was invited to complete a concept mapping process that included brainstorming the factors that are associated with rural food access, sorting and organizing the factors into similar domains, and rating the importance of policies and research to address these factors. As a last step, RFAWG members convened to interpret the data and establish research recommendations. Results Seventy-five participants in the brainstorming exercise represented the following sectors: non-extension research (n = 27), non-extension program administration (n = 18), “other� (n = 14), policy advocacy (n = 10), and cooperative extension service (n = 6). The brainstorming exercise generated 90 distinct statements about factors associated with rural food access in the United States; these were sorted into 5 clusters. Go Zones were established for the factors that were rated highly as both a priority policy target and a priority for research. The highest ranked policy and research priorities include strategies designed to build economic viability in rural communities, improve access to federal food and nutrition assistance programs, improve food retail systems, and increase the personal food production capacity of rural residents. Respondents also prioritized the development of valid and reliable research methodologies to measure variables associated with rural food access. Conclusions This collaborative, trans-disciplinary, participatory process, created a map to guide and prioritize research about polices to improve healthy, affordable food access in rural communities