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The current study investigates the discursive strategies used by Jewish Israeli women when telling stories of self-empowerment involving interpersonal tension with authority figures. Our corpus is based on in-depth interviews with thirty women aged fifty to ninety-three from the southern city of Beer Sheva, Israel. We identified forty-two narratives manifesting interpersonal tension, mostly with authority figures. Drawing on the theoretical framework of narrative analysis, we conduct a performance-based, pragmatic microanalysis of four stories through which we demonstrate an ensemble of strategies paramount in shaping and contesting power relations, including use of direct reported speech, address and reference terms, and code-switching. By telling their stories, our storytellers mobilized the storytelling event as an occasion to perform a self-empowering move through which they subverted the frameworks of authority not only on a local level in the narrated and storytelling events but potentially also on a broader societal level, disrupting hegemonic asymmetries. (Power relations, narratives, self-empowerment, direct reported speech, code-switching, terms of address, terms of reference)

We examined the interplay between familial risk and the quality of the home environment and the intermediate role of cognitive functioning in the development of attention-deficit hyperactivity disorder (ADHD). Participants were 99 boys and their parents (M age = 7.34 years, SD = 0.23), who have been followed longitudinally since birth; 62 participants were followed until adolescence (M age = 13.5 years, SD = 0.95). We found that differential susceptibility to home environment in early childhood predicted the cognitive functioning (decreased executive function [EF] and increased intrasubject variability [ISV]) at elementary-school age. Specifically, in a lower quality home environment, those at high familial risk showed poor cognitive functioning (i.e., low EF and high ISV) at elementary-school age but under a supportive environment showed high cognitive functioning (i.e., high EF and low ISV), outperforming their peers at low familial risk. Moreover, child EF, but not ISV, was involved in a developmental path leading to an ADHD phenotype; it was found to mediate the relation between the early risk level (i.e., the interaction between familial risk and home environment) and child ADHD symptoms. A preliminary analysis suggests that EF may have a longitudinal effect on ADHD symptoms in adolescence; after controlling for the level of symptoms at elementary-school age, children with low levels of EF showed a significant increase in their symptoms over time. In general, our results propose a plausible mechanism that explains how the familial risk for ADHD could be translated into actual symptoms among children, at least in the case of boys.

Using a bioecological perspective, this longitudinal study examined the contribution of child and environmental factors to the prediction of reading achievement at age 7. Participants were 99 boys and their parents. Child factors included 24-month temperament (reactivity and self-regulation), 36-month language level, and 7-year ADHD symptoms; environmental factors included quality of the home environment (54 months), maternal education, and learning disability (LD) in the family. There were direct and indirect pathways to reading achievement. Direct pathways included language skills, home environment, ADHD symptoms, and LD in the family. Unexpectedly, the direct pathway from self-regulation was negative. Indirect pathways included self-regulation, maternal education, and reactivity. Given the stability of the trajectory of reading skills and academic performance from first grade onward, the early identification of those children most at risk for reading difficulties has implications for the type of interv...

An electrochemical approach was devised for detecting DNA damage and differentiating two DNA damage mechanisms, which is important to the design of new chemotherapeutics. This approach combined two platforms, based on the detection of base damage and DNA strand cleavage. In this work, our approach was demonstrated for the detection of cisplatin-induced DNA damage and the enhancement effects of two electron donors, N,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD) and reduced graphene oxide (rGO). Our results demonstrated that TMPD enhanced DNA strand cleavage, supporting the proposed dissociative electron transfer mechanism. While rGO, which is an efficient electron donor, failed to show any enhancement (suggesting the lack of free-radical generation), overall, this electrochemical approach could be implemented for discovering next-generation DNA damage-based chemotherapy drugs.

There is a need for an accurate end-of-life indicator for packaged food (meat, seafood, dairy food etc.) beyond a simple “best use by” date on the food package. In this work, we propose a low cost solution by repurposing the food’s barcode as a colorimetric sensor array to monitor food condition. A smart phone camera is used to read color information from the sensor barcode for quantitative estimate of the food aging and quality. The sensor is based on cross-reactive vapor sensitive dyes encapsulated in resin microbeads, which are impregnated onto a low cost paper substrate in a barcode pattern. The entire sensor platform is validated by accurately monitoring chicken aging and eventual spoilage under different temperature conditions. The proposed food diagnostics platform has the potential to reduce food waste and eliminate food-borne illness.

Carbon nanomaterials (CNMs) have outstanding mechanical and electrical properties, making them ideal candidates for improving conventional cardiac tissue scaffolds. The improved cardiac tissue constructs have the potential to advance drug discovery and eventually allow for myocardial tissue regeneration, improving the treatment of heart diseases. This review first outlines the major research directions in the treatment of heart diseases, including surgical methods and pharmacological therapies, as well as gene and cell therapy. Afterwards, the review focuses on the use of CNMs in the construction of scaffolds for engineering cardiac tissue constructs, which could offer promising solutions to address the challenges in cell therapy. A series of studies in the past five years have shown that the incorporation of CNMs in tissue scaffolds enhances the survival, retention, organization, and physiological functions of cardiomyocytes.

Extreme levels of certain temperament traits can be early markers of different developmental pathways of attention-deficit/hyperactivity disorder (ADHD). However, the long-term utility of using these traits as predictors of ADHD is not fully known. This study includes 64 male adolescents (M age = 13.5), who have been followed since birth as part of a longitudinal study. The primary aim was to test effortful control (EC), activity level, and anger, measured in early childhood - both with mother's reports and laboratory assessments -as predictors of ADHD symptoms in adolescence. Further, we investigated the specificity of this prediction to the different ADHD symptom domains. The results demonstrated that early temperament dimensions of EC and activity level were predictive of ADHD symptoms about 10 years later, when the participants reached adolescence. Moreover, activity level showed specificity only to hyperactivity-impulsivity symptoms whereas EC was a predictor of the two symptom domains. Anger had a predictive correlation with ADHD symptoms; however, it did not have a unique predictive contribution. These results emphasize the relevance of EC and activity level in the developmental course of ADHD. Identification of early risk factors can lead to more efficient design and implementation of intervention programs.

Current diagnostic systems used in clinical settings to detect protein biomarkers require highly trained experts, large volumes of blood samples, and long turnaround times. There is an immense need for a low-cost and accurate point-of-care-testing (POCT) device for home monitoring of protein biomarkers for global pandemics such as heart failure (HF). The integration of highly sensitive carbon nanotube (CNT) thin film (CNT-TF) impedance sensors with the electrochemical impedance spectroscopy (EIS) technique is a promising platform to actualize POCT systems for home use. Herein, we report such a system, NanoBot, which allows the label-free and wash-free detection of the HF antigen biomarker B-type natriuretic peptide (BNP) in blood plasma. The NanoBot system consists of two parts: a disposable test strip and a miniature electronic readout unit. The NanoBot exhibited reasonable accuracy and precision, a clinically relevant limit of detection (LOD) as low as 16 pg mL-1, a linear detection range from 0-4000 pg mL-1 and excellent correlation with a reference standard fluorescent immunoassay (FIA). A pilot clinical study with patient-derived blood plasma validated the NanoBot's strong performance compared to that of Alere Triage®, with an interclass correlation coefficient (ICC) of 98% and a square of correlation coefficient (CC) of 0.95. Furthermore, unlike the Alere Triage® that requires more than 250 μL of blood collected via venipuncture, the NanoBot only requires 50 μL of blood. Collectively, the NanoBot's high sensitivity, accuracy, precision, and self-calibration characteristics signify its promising potential as a POCT platform for heart failure diagnosis in home use.

In this work, we present a disposable paper-based optical sensor arranged as barcode for monitoring food spoilage. The color-changing barcode is embedded in the food packaging and monitored using smart phone. The color change of different optical sensing dyes that make up the barcode is due to the emission of volatile organic compounds (VOCs) from food. Different geometric shapes are assigned to each sensing dye for identification. The sensor fabrication is low-tech and easy to perform. A smart phone quantifies the color change in the barcode food sensor, which provides a non-contact metric of food freshness/spoilage.

We demonstrate dissolved ammonia (NH3) sensing in complex mixtures using an optoelectronic sensor comprising a composite sensing material based on a metalloporphyrin zinc tetraphenylporphyrin (ZnTPP) and spectroscopic detection. The metalloporphyrin dye is incorporated within ion-exchange polymeric microbeads arranged in a microfluidic array. Spectroscopic analysis at multiple wavelengths allows sensitive detection in complex backgrounds. The sensor shows preferential sensitivity to ppm levels of concentrations of NH3 dissolved in water, as well as in human saliva, making it relevant for medical diagnostic applications (e.g. detection of stomach bacterial infections). The microfluidic platform and a miniaturized optical arrangement provide a potential for the development of a portable low-power sensor for detection of dissolved ammonia for a variety of applications.

We present a microfluidic optoelectronic cross-reactive sensor based on a novel composite material for selective detection of dissolved CO 2 . A microfluidic device contains an array of micro-wells filled with ion-exchange polymeric microbeads doped by halochromic dyes paired to quaternary ammonium cations. The sensor configuration allows incorporation of virtually any combination of halochromic ion-pairs, providing a route for cross reactive sensing. A versatile optical arrangement based on a white LED and a miniature portable USB spectrometer allows recording optical spectra, which are easily translated into electronic readouts. Rather than monitoring response at a particular absorption or emission wavelength of the dye, data acquisition is performed over a broad continuous spectrum. This results in a rich multidimensional readout useful for ultrasensitive detection. The sensor provides distinctive responses to different concentrations of dissolved CO 2 , with no cross sensitivity to other sources of acidity. Our findings could lead to the development of a cost-effective, lightweight, and low-power sensor for detection of dissolved CO 2 for a variety of applications.

Children of mothers with attention-deficit/hyperactivity disorder (ADHD) have an increased genetic and environmental risk for ADHD. The unique and interactive contributions of a maternal dopamine receptor gene (DAT1), maternal ADHD symptoms (hyperactive- impulsive, inattentive), and home atmosphere to the prediction of ADHD symptoms (hyperactive- impulsive, inattentive) in 7- year-old boys (N = 96) were examined using data from a longitudinal study of familial risk for ADHD. During the first 6 months of the study, mothers and their spouses completed a questionnaire about the mother’s ADHD symptoms. Home atmosphere questionnaire data were collected 4 years later. At the 7-year assessment, mothers reported on their child’s ADHD symptoms. Negative home atmosphere was significantly associated with child hyperactive-impulsive and inattentive symptoms. Maternal inattentive symptoms were significantly correlated with both child symptom dimensions. Regression models, with child genotype and maternal education controlled, showed main effects for maternal inattentive symptoms, maternal DAT1 10/10 genotype, and home atmosphere in the prediction of child inattentive symptoms. Only home atmosphere predicted child hyperactive-impulsive symptoms. There was a significant home atmosphere x maternal hyperactive-impulsive symptoms interaction in the prediction of child hyperactive-impulsive symptoms. Boys with higher levels of symptoms came from homes characterized by higher levels of negative atmosphere and had mothers with higher levels of hyperactive-impulsive symptoms. There was also a trend (p = 0.075) for a maternal DAT1 x home atmosphere interaction. Boys with higher levels of inattentive symptoms came from homes with higher levels of negative atmosphere and had mothers with the homozygous 10/10 genotype. The maternal heterozygous 9/10 genotype did not predict child symptoms.

We present a gastric gas sensor based on conjoined dual optical fibers functionalized with sensitive optical dyes for sensing gases in both fluidic and gaseous environments. The sensor aims to sense various concentrations of carbon dioxide (CO2) and ammonia (NH3), which are two significant biomarkers of H. pylori infection in the stomach. It is known that CO2 and NH3 are released during the hydrolysis of urea by H. pylori, a bacterium that may cause stomach cancer with relatively high probability. CO2 and NH3 sensitive optical dyes, cresol red ion pair and zinc tetraphenylporphyrin, are embedded in silica beads and then functionalized onto the thin PDMS-coated fiber tip. Each type of dye provides a unique spectral emission response when excited with light ranging from 450 to 700 nm. Two SMA connector legs of the as-functionalized sensor are connected to an external light source for illumination and a ultraviolet-visible-near infrared (UV-Vis-NIR) spectrometer for signal collection/readout. To perform the measurements, one fiber illuminates while the other fiber collects the back-scattered light and feeds it to the UV-Vis-NIR spectrometer to measure the change in light spectrum as a function of CO2 or NH3 concentration. This method is easy and flexible and achieves ppm level sensitivity to targeted gas analytes. The proposed sensor can be integrated into a customized tethered capsule for adjunctive diagnosis of H. pylori infection to improve the accuracy of visual endoscopic inspection. Scopus

Real-world samples contain reducing and oxidizing chemical agents as well as large and small (bio)molecules, which are polar or nonpolar in nature. Sensing nonpolar analytes, which is of paramount importance for a wide variety of applications, is generally more difficult to achieve than sensing polar analytes. Here, we report on empirical observations of a unique polycyclic aromatic hydrocarbon derivative, referred as PAH-A, whose structure has a triangular-shaped aromatic core (with a carbon number of 60) and contains hydrophobic mesogens terminated with hydrophobic alkyl chains. We show that films made of PAH-A enable excellent sensitivity to nonpolar analytes, compared to polar analytes, in a setting of 5−40% counteracting relative humidity. This finding is based on monitoring the changes in the physical/optical properties of thin PAH-A films upon exposure to nonpolar and polar analytes, by means of quartz crystal microbalance and spectroscopic ellipsometry measurements. A comparison with other polycyclic aromatic hydrocarbon derivatives with different cores or organic functionalities is provided and discussed.

A cross-reactive array of polycyclic aromatic hydrocarbons and single wall carbon nanotube bilayers was designed for the detection of volatile organic compounds (tentatively, hexanal and 5-methyl-undecane) that identify the presence of disease in the exhaled breath of patients with multiple sclerosis. The sensors showed excellent discrimination between hexanal, 5-methyl-undecane, and other confounding volatile organic compounds. Results obtained from a clinical study consisting of 51 volunteers showed that the sensors could discriminate between multiple sclerosis and healthy states from exhaled breath samples with 85.3% sensitivity, 70.6% specificity, and 80.4% accuracy. These results open new frontiers in the development of a fast, noninvasive, and inexpensive medical diagnostic tool for the detection and identification of multiple sclerosis. The results could serve also as a launching pad for the discrimination between different subphases or stages of multiple sclerosis as well as for the identification of multiple sclerosis patients who would respond well to immunotherapy.

T cell development in the thymus is controlled by thymic epithelial cells (TE). While it is accepted that TE interact with maturing T cells, the mechanisms by which they trigger 'death by neglect' of double-positive (DP) thymocytes are poorly understood. We and others have demonstrated a role for TE-derived glucocorticoids (GCs) in this process. We have studied TE-induced apoptosis using an in vitro system based on co-culturing a thymic epithelial cell line (TEC) with DP thymic lymphoma cells or thymocytes (DP thymic cells). Here, we demonstrate that nitric oxide (NO*) is also involved in this death process. The inducible nitric oxide synthase (iNOS) inhibitors N(G)-methyl-L-arginine and 1,4-PBIT attenuated TEC-induced apoptosis of DP thymic cells. Co-cultivation of TEC with DP thymic cells increased the expression of iNOS in TEC. A concomitant increase in NO* was detected by staining with DAF-FM diacetate. Moreover, the iNOS-regulating cytokines IL-1alpha, IL-1beta and IFNgamma were up-regulated upon interaction of TEC with DP thymic cells. Neutralizing IL-1R or IFNgamma reduced TEC-induced apoptosis of DP thymic cells. Cardinally, NO* synergizes with GCs in eliciting apoptosis of DP thymic cells. Our data indicate that a cross-talk between DP thymic cells and TEC is required for proper induction of iNOS-up-regulating cytokines with a subsequent increase in iNOS expression and NO* production in TEC. NO*, in turn, cooperates with GCs in promoting death by neglect. We suggest that NO* together with GCs fine-tune the T cell selection process.

Cancer is a leading health hazard, and lung cancer is its most common form. Breath testing is a fast, noninvasive diagnostic method which links specific volatile organic compounds (VOCs) in exhaled breath to medical conditions. Arrays of sensors based on carbon nanotubes (CNTs) could in principle detect cancer by differentiating between the VOCs found in the breath of healthy and sick persons, but the notoriously low sensitivity of CNT sensors to nonpolar VOCs limits their accuracy. In this study, we have achieved a marked improvement of the sensitivity and selectivity of random networks (RNs) of CNT chemiresistors to nonpolar VOCs by functionalizing them with self-assembled, spongelike structures of discotic hexa-peri-hexabenzocoronene (HBC) derivatives. We observed swelling of the organic film by monitoring the changes of organic film thickness during exposure and propose that the expansion of the spongelike organic overlayer creates scattering centers in the underlying RN-CNTs by physically distancing the CNTs at their intersections. The results presented here could lead to the development of robust sensors for nonpolar VOCs of cancer breath, which have hitherto been difficult to trace.

Epidermal pH is an indication of the skin's physiological condition. For example, pH of wound can be correlated to angiogenesis, protease activity, bacterial infection, etc. Chronic nonhealing wounds are known to have an elevated alkaline environment, while healing process occurs more readily in an acidic environment. Thus, dermal patches capable of continuous pH measurement can be used as point-of-care systems for monitoring skin disorder and the wound healing process. Here, pH-responsive hydrogel fibers are presented that can be used for long-term monitoring of epidermal wound condition. pH-responsive dyes are loaded into mesoporous microparticles and incorporated into hydrogel fibers using a microfluidic spinning system. The fabricated pH-responsive microfibers are flexible and can create conformal contact with skin. The response of pH-sensitive fibers with different compositions and thicknesses are characterized. The suggested technique is scalable and can be used to fabricate hydrogel-based wound dressings with clinically relevant dimensions. Images of the pH-sensing fibers during real-time pH measurement can be captured with a smart phone camera for convenient readout on-site. Through image processing, a quantitative pH map of the hydrogel fibers and the underlying tissue can be extracted. The developed skin dressing can act as a point-of-care device for monitoring the wound healing process.

The mechanisms by which glucocorticoid receptor (GR) mediates glucocorticoid (GC)-induced apoptosis are unknown. We studied the role of mitochondrial GR in this process. Dexamethasone induces GR translocation to the mitochondria in GC-sensitive, but not in GC-resistant, T cell lines. In contrast, nuclear GR translocation occurs in all cell types. Thymic epithelial cells, which cause apoptosis of the PD1.6 T cell line in a GR-dependent manner, induce GR translocation to the mitochondria, but not to the nucleus, suggesting a role for mitochondrial GR in eliciting apoptosis. This hypothesis is corroborated by the finding that a GR variant exclusively expressed in the mitochondria elicits apoptosis of several cancer cell lines. A putative mitochondrial localization signal was defined to amino acids 558–580 of human GR, which lies within the NH2-terminal part of the ligand-binding domain. Altogether, our data show that mitochondrial and nuclear translocations of GR are differentially regulated, and that mitochondrial GR translocation correlates with susceptibility to GC-induced apoptosis.

"Negative selection" and "death by neglect" are governed by apoptotic processes occurring in the thymus that shape the repertoire of maturing T cells. We have previously developed an in vitro model that recapitulates "death by neglect": Co-cultivation of double positive (DP) thymocytes or thymic lymphoma cells (PD1.6) with thymic epithelial cells (TEC) caused TcR-independent apoptosis of the former. We further demonstrated that this apoptosis could be attenuated by aminoglutethimide, an inhibitor of steroid synthesis, suggesting a role of TEC-derived glucocorticoids (GC) in this death process. We have now substantiated the role of the GC-glucocorticoid receptor (GR) axis by using a GC-resistant subline (PD1.6Dex(-)) obtained from the GC-sensitive PD1.6 cells by repeated exposures to increasing doses of dexamethasone (Dex). The PD1.6Dex(-) cells barely express GR and are much less sensitive to TEC-induced apoptosis. Re-expression of GR in PD1.6Dex(-) cells restored their sensitivity to both Dex and TEC, highlighting the central role of GR in these apoptotic processes. Likewise, repeated exposures of PD1.6 cells to TEC led to the selection of TEC-resistant cells (PD1.6TEC(-)) that are insensitive to corticosterone and less sensitive to Dex, though their GR level was only moderately reduced. This is in line with the low levels of corticosterone secreted by TEC. Altogether, our data show that TEC eliminates DP thymic lymphoma cells in a GR-dependent manner and modulates the GC sensitivity of the surviving cells.

Paper, a cheap and ubiquitous material, has great potential to be used as low-cost, portable and biodegradable platform for chemical and biological sensing application. In this paper, we are exploring a low-cost, flexible and reliable method to effectively pattern paper for capturing optical dyes and for flow-based delivery of target samples for colorimetric chemical sensing. In this paper, we target the detection of ammonia (NH 3 ) and carbon dioxide (CO 2 ), two of the important environmental and health biomarkers. By functionalizing the paper platform with diverse cross-reactive dyes sensitive to NH 3 and CO 2 , their selective sensing within a certain pH range, as well as their detection at different concentrations can be achieved. The images of paper based device were captured by a flatbed scanner and processed in MATLAB ® using a RGB model and PCA for quantitative analysis. Paper based devices with readout using ubiquitous consumer electronic devices (e.g. smartphones, flatbed scanner) are considered promising approaches for disease screening in developing countries with limited resources.

We present a microfluidic optoelectronic sensor for saliva diagnostics with a potential application for non-invasive early diagnosis of stomach cancer. Stomach cancer is the second most common cause of cancer-related deaths in the world. The primary identified cause is infection by a gram-negative bacterium Helicobacter pylori. These bacteria secrete the enzyme urease that converts urea into carbon dioxide (CO2) and ammonia (NH3), leading to their elevated levels in breath and body fluids. The proposed optoelectronic sensor will detect clinically relevant levels of CO2 and NH3 in saliva that can potentially be used for early diagnosis of stomach cancer. The sensor is composed of the embedded in a microfluidic device array of microwells filled with ion-exchange polymer microbeads doped with various organic dyes. The optical response of this unique highly diverse sensor is monitored over a broad spectrum, which provides a platform for cross-reactive sensitivity and allows detection of CO2 and NH3 in saliva at ppm levels.

Eosinophils contain in their granules eosinophil cationic protein (ECP) and other basic proteins that have been implicated in immunity to parasites and pathophysiology of chronic allergic responses. In a model of eosinophil degranulation, we show that eosinophils release ECP upon short-term GM-CSF priming and stimulation with either platelet-activating factor (PAF) or the anaphylatoxin C5a, but not eotaxin. Restimulation with the same agonist (PAF or C5a) was unsuccessful as assessed by monitoring intracellular calcium concentration and ECP release. In contrast, upon an intermediate washing step, eosinophils rapidly transduced PAF and C5a signals followed by significant ECP releases. Ligand-binding studies demonstrated that only a proportion of PAF receptors is internalized upon cell stimulation and that washing of the cells removes the agonist from the cell surface. Upon repetitive stimulation, eosinophils with less than 50% of the original ECP content were obtained. Such eosinophils did not increase cellular ECP levels even in the presence of the eosinophil survival factor GM-CSF in overnight cultures. In vivo studies revealed that eosinophils always express detectable amounts of ECP under chronic inflammatory conditions. In conclusion, we have shown that eosinophils maintain their capacity to degranulate upon repetitive stimulation with the same agonist as long as the receptor is not occupied from a previous stimulation. The cellular content of ECP appears to be a no limiting factor in the case of repetitive stimulation, implying that mature eosinophils may not require a significant ECP resynthesis.

We have previously described an in vitro system in which thymic epithelial cells induce apoptosis in CD4 + 8 + thymocytes or thymic lymphoma cells, in the absence of an exogenous antigen. A thymic epithelial cell line (TEC) recapitulated the response, by inducing apoptosis in CD4 + 8 + thymocytes of the thymic lymphoma clone, PD1.6. The present study pursues the involvement of the T-cell receptor (TcR) in the response of PD1.6 to TEC. TcR cross-linking did not cause apoptosis of PD1.6, although it induced tyrosine phosphorylation of p95 vav . In contrast, TEC did not induce phosphorylation of p95 vav , but induced apoptosis of PD1.6 cells. These results suggest that TcR-evoked signals are not involved in TEC-induced apoptosis of PD1.6. Intracellular calcium chelation, using BAPTA-loaded PD1.6 cells, diminished TEC-induced apoptosis. Protein kinase C depletion in PD1.6 cells augmented their apoptotic response to TEC. Thus, the response of PD1.6 to TEC is calcium-dependent and inhibited by PKC. Likewise, the apoptotic response of PD1.6 to A23187 was abrogated by PKC activation. PD1.6 cells may represent an immature double positive thymocyte population, which does not undergo negative selection. The interaction of PD1.6 with TEC may thus serve as a model for the TcR-independent ‘Death by Neglect’, which takes place in the thymus during thymocyte development.

We present a microfluidic optoelectronic sensor for detection of dissolved CO2 in aqueous samples. The sensor contains an array of wells embedded in a microfluidic device and filled with ion-exchange polymeric microbeads doped with halocromic dyes. We have developed a simple procedure for microbeads deposition that allows incorporation of virtually any combination of halocromic dyes, providing a route for cross-reactive sensing. Due to a versatile optical arrangement, using LEDs and photodiodes, optical signals are easily translated into electronic readouts. We demonstrate the sensor ability to provide distinct responses to different concentrations of dissolved CO2. Moreover, the sensor shows no cross sensitivity to acidity not related to dissolved CO2.

In her article "Nostalgia in Oral Histories of Israeli Women" Yael Zilberman explores the narration of nostalgia of elderly women about the city of Be'er Sheva. In their narration, the subjects of the study create textual and spatial practices which are engendered and create analogies between the city, their maturing/ed bodies, and by-gone youth. Further, the grief owing to the perceived condition of the city intensifies the idealized description of the city and the longing for its past. Zilberman's study brakes new ground in that the study of urban experience within folklore is a lesser explored field as the urban environment is considered by many folklore scholars as a deterioration folklore in the country side. Since the 1980s, however, urban folklore has been gaining scholarly attention and women and more so elderly women represent one such group. Yael Zilberman, "Nostalgia in Oral Histories of Israeli Women" page 1 of 2 CLCWeb: Comparative Literature and Culture 14.4 (2012)

Incubation of cultured ventricular cardiomyocytes with high oligomycin concentrations (100 micrograms/ml), either alone or combined with 2-deoxyglucose (20 mM), led to the rapid depletion of cellular ATP. Inositol (poly)phosphate production decreased, and 6-keto PGF1 alpha production was increased. In cells depleted of ATP, either by low oligomycin concentrations or by sodium azide, 6-keto PGF1 alpha was not appreciably increased. There was a 25% rise in the release of fatty acids from the sn-2 position in glycerophospholipids. We suggest that oligomycin at high concentrations causes the release of free arachidonic acid from phospholipids either by non-PIP2-specific PLC and DG lipase or by phospholipase D, phosphatidic acid phosphatase and DG lipase. The effect is unrelated to decreased cellular ATP content.

In this study, we introduce a novel synthetically designed polycyclic aromatic hydrocarbon (PAH) chemFET. The chemFET device operates by employing voltage dependent back-gate measurements, wherein the drain current (I d ) is monitored while the gate voltage (V g ) applied to the device is swept backward and forward between −40V and +40V. Using this device, we demonstrate that an extremely selective e-nose can be developed by extracting the most suitable features from the I d -V g characteristic curves of a single chemFET. The accuracy of the identification of eight different volatile organic compounds (VOCs) surpassed 91%.

In the present work, we introduce a cross-reactive array of synthetically designed polycyclic aromatic hydrocarbons (PAH) and single-walled carbon nanotube (SWCNT) bilayers and demonstrate the huge potential of the array in discriminating between polar and nonpolar volatile organic compounds (VOCs), as well as between the different VOCs from each subgroup. Using appropriate combinations of PAH/SWCNT sensors, we demonstrate that high sensitivity and accuracy values can be obtained for discriminating polar and nonpolar VOCs in samples with variable humidity levels (5-80% RH). The same array of sensors exhibited self-learning capabilities that facilitated exchanging information about environmental properties under observation. The results presented here could lead to the development of a cost-effective, lightweight, low-power, and non-invasive tool for a widespread detection of VOCs in real-world environmental, security, food, health, and other applications.

Eighty percent of the lymphoid cells in the murine thymus are premature CD4+8+ (double positive) thymocytes. The vast majority of the double-positive cells do not maturate and die in the thymus. Although these cells are subjected to thymic selection processes, their activation competence has been an enigma. We have separated out CD4+8+ cells and studied their early and late responses to several mitogens. Concanavalin A, anti-CD3 (145-2C11) or anti-Thy1 (G7) monoclonal antibodies enhanced phosphoinositide turnover in double-positive thymocytes. However, DNA synthesis in the mitogen-stimulated cells was only accomplished if IL-2 or IL-4 was added. Alternatively, DNA synthesis could be induced by the calcium ionophore A23187 and phorbol myristate acetate (PMA). The latter mode of activation did not require the addition of exogenous lymphokines. CD4+8+ thymocytes did not secrete IL-2 or IL-4 following activation by either mitogens or A23187 and PMA. These findings demonstrate that CD4+8+ thymocytes resemble mature T cells in their ability to respond with DNA synthesis when activated by T-cell mitogens and IL-4 as well as IL-2. The results also delineate the difference between receptor mediated mitogenesis and pharmacological stimulation.

The effects of staurosporine, a protein kinase inhibitor, on the signal transduction and proliferation of thymocytes were studied. Signal transduction in response to Concanavalin A (Con A) as well as Concanavalin A (Con A)-induced augmentation of [ 3 H]inositol incorporation into phospholipids were inhibited by staurosporine (≥10 −8 M). Staurosporine inhibited thymocyte proliferation in response to Con A in the presence or absence of the phorbol ester, phorbol myristate acetate (TPA) (10 nM). This inhibition was observed regardless of whether staurosporine was added together with Con A or 3 hr later. High concentrations of staurosporine (>10 −8 M) inhibited thymocyte proliferation induced by the calcium ionophore A23187 and the phorbol ester TPA, whereas lower concentrations of the inhibitor (≤10 −8 M) enhanced thymidine incorporation in response to these activators. This dual effect of staurosporine was also observed in the presence of the staurosporine-related kinase inhibitor, K252a. In contrast, the tyrosine kinase inhibitor, tyrphostin AG490, inhibited the response to A23187 and TPA at all concentrations of the inhibitor and no augmentation was seen. Interleukin 2 (IL-2)-driven mitogenesis in IL-2-dependent cells was also inhibited by staurosporine. We suggest that the inhibition of thymocyte proliferation by staurosporine results from inhibition of both protein kinase C and tyrosine kinase: the augmentation of the response to A23187 and TPA results from inhibition of protein kinase C. Inhibition of signal transduction as well as inhibition of IL-2-driven mitogenesis result from inhibition of tyrosine kinase.

Mouse medullary thymocytes have specific receptors for 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). The mitogenic stimulation of these cells by phytohemagglutinin in the presence or absence of the phorbol ester TPA is inhibited by 1,25(OH) 2 D 3 . The calcium ionophore A23187 did not reverse the inhibition by 1,25(OH) 2 D 3 of phytohemagglutinin. Stimulation of thymocytes with either TPA or A23187 alone did not result in proliferation. Co-stimulation of the thymocytes with TPA and A23187 induces cell proliferation. 1,25(OH) 2 D 3 markedly enhanced the TPA and A23187-induced cell proliferation even when added 4 h after the initiation of the culture. In contrast, DNA synthesis by thymocytes incubated for 4 h in the presence of TPA and A23187 and then cultured in medium containing 1,25(OH) 2 D 3 but in the absence of both TPA and A23187, was inhibited by 1,25(OH) 2 D 3 . The extent of inhibition was comparable to the inhibition of lectin-induced stimulation by the hormone. Using monoclonal antibodies to neutralize IL-2 and block IL-2 receptors we showed that 1,25(OH) 2 D 3 enhanced the IL-2-independent component of the A23187- and TPA-induced mitogenesis. In conclusion: (1) The nature and presence of the mitogenic signal determines whether 1,25(OH) 2 D 3 enhances or inhibits thymocyte stimulation. (2) Both stimulatory and inhibitory actions of 1,25(OH) 2 D 3 seem to take place at points distal to the initial increase in intracellular calcium or activation of protein kinase C.

Glucocorticoids (GCs) are used for treatment of various hematopoietic malignancies owing to their ability to induce apoptosis. A major obstacle in leukemia therapy is the emergence of GC-resistant cells. Hence, combinatory treatment protocols should be developed that convert GC-resistant leukemia cells into sensitive ones. Here we demonstrate that the broad-acting kinase inhibitor staurosporine (STS) confers GC-sensitivity on GC-resistant T lymphoma cells expressing elevated levels of either Bcl-2 or Bcl-XL, but not on GC-resistant myelogenic leukemia cells expressing Mcl-1 in addition to Bcl-2 and/or Bcl-XL. In T lymphoma cells, STS induces the expression of the pro-apoptotic orphan receptor Nur77 that overcomes the anti-apoptotic effect of Bcl-2, thus enabling GCinduced apoptosis. However, in the myelogenic leukemia cells, STS does not upregulate Nur77. In these cells, the glucocorticoid receptor (GR) is rapidly downregulated by GC and the anti-apoptotic Mcl-1 protein is upregulated by STS, thereby leading to an even more resistant phenotype. Altogether, our data provide a molecular basis for the differential apoptotic response of T lymphoma versus myelogenic leukemia cells to STS and GC. The former being sensitized to GC-induced apoptosis by STS, whereas in the latter, STS intensifies GC resistance. The cell type specific responses should be taken into consideration when combinatory therapy is used for treating hematopoietic malignancies.

Recent data cast new light on the mechanisms by which glucocorticoids (GCs) elicit apoptosis of thymocytes and leukemia cells. Here we attempt to integrate recent studies by others and us, which provide a novel insight to this apoptotic process. In the last few years it was made clear that there is a tight cooperation between genomic and non-genomic effects exerted by GC receptors (GRs). GC invokes major alterations in the gene expression profile through GR-mediated transactivation and transrepression, which ultimately tip the balance between pro-survival and pro-apoptotic proteins. Although essential in shaping the cell's proteome, these genomic effects are insufficient to elicit apoptotic death and additional signals are required for activating the pro-apoptotic proteins. Several non-genomic effects have been described that occur immediately following exposure to GC, which are imperative for the induction of apoptosis. We have recently observed that GC induces instant GR translocation to the mitochondria in GC-sensitive, but not in GC-resistant, T lymphoid cells. This response contrasts the nuclear translocation of GR occurring in both cell types. We propose that the sustained elevation of GR in the mitochondria following GC exposure is crucial for triggering apoptosis.

Thymic lymphomas and hybridomas vary in their sensitivity to dexamethasone (DEX). Identical variance has been demonstrated in our laboratory for apoptosis of such cells by primary thymic epithelial cells or a cell line (TEC). We have also shown that apoptosis induced by TEC was partially mediated by TEC-derived glucocorticoids (GC). We studied the responses of various thymic lymphomas and hybridomas to TEC and DEX. Of these cells, PD1.6 and 2B4 were sensitive whereas B10 were relatively resistant to either inducer. In the present study we found that TEC and DEX synergize in inducing B10 cell apoptosis. B10 cells could also undergo apoptosis by TEC, conditional upon the presence of a TEC-sensitive cell (PD1.6 or 2B4). Contact between TEC and B10 was essential for apoptosis to occur. Thus, TEC may provide two signals, one mediated by GC and the other requiring cell to cell contact. We then analyzed the involvement of co-stimulatory or adhesion molecules in the TEC-induced apoptosis of thymic lymphoma cells. Soluble anti-CD44 antibodies but not anti-CD18, CD2 or CD28, inhibited TEC-induced apoptosis of PD1.6. Dimerization of CD44 by immobilized antibodies augmented DEX-induced apoptosis of all the lymphomas tested. CD44 cross-linkage up-regulated expression of the pro-apoptotic protein Bax, and down-regulated the anti-apoptotic protein, Bclx(L), in the presence of DEX. Taken together, the data suggest that CD44 enhances the apoptotic response of T lymphoma cells to DEX, and that CD44 modulates TEC-induced apoptosis of thymic lymphomas.

We have studied the mechanisms involved in TcR-independent apoptosis of radiation leukemia virus (RadLV)-transformed thymocyte clones induced by a thymic epithelial cell line (TEC). TEC induced apoptosis of an immature CD4 + 8 + 3 + (PD1.6) but not of a CD4 − 8 − 3 − (B10) thymocyte clone. TEC-derived conditioned medium did not mimic the signal induced by TEC in PD1.6 cells. However, the TEC-resistant clone B10 apoptosed in response to TEC, provided that PD1.6 cells were also present in the culture. This effect on bystander cells suggests that a secreted factor was involved. The involvement of glucocorticoid hormones as potential mediators was addressed. PD1.6 cells apoptosed in response to dexamethasone or a cell-permeating analog of cAMP, while B10 cells were relatively resistant to dexamethasone. TcR cross-linking inhibited both TEC- and dexamethasone- but not cAMP-induced apoptosis. Aminoglutethimide and Ru38486 inhibited TEC-induced apoptosis of PD1.6 cells, whereas Ru28318 had a negligible effect. The results suggest that steroid hormones are involved in TcR-independent apoptosis of immature double-positive thymocyte clones induced by TEC.

Cortical and medullary thymocytes can be separated from each other by virtue of the fact that only cortical thymocytes bear peanut agglutinin (PNA) receptors. The mitogenic responses of subpopulations of thymocytes were studied. We have confirmed the results of Conlon et al. [(1982) J. Immun. 128, 797-801], that lectin-induced stimulation of unseparated cells, and PNA- but not PNA+ thymocytes, results in DNA synthesis. In contrast, both subpopulations, as well as unseparated cells, synthesize DNA in response to the calcium ionophore A23187 in the presence of the phorbol ester TPA, suggesting an impairment of signal transduction in PNA+ cells. However, comparable amounts of inositol phosphates were accumulated in PNA- and PNA+ thymocytes in response to Concanavalin A (Con A). We suggest that mitogenic lectins generate a third signal in addition to elevation of intracellular free calcium concentration and activation of protein kinase C. This signal is generated in PNA- but not in PNA+ thymocytes and is obligatory for lectin-induced stimulation.

In mixed micelles of phospholipids and bile salts, the phospholipids are arranged as a flat bilayer with bile salts distributed along the hydrophobic edges. The linewidths of signals in the proton magnetic resonance spectra of such mixed micelles depend strongly on the size of the micelles, which is a function of the molar ratio of the components. The signals in the spectra of such mixed micelles are much broader than the corresponding signals in the much larger, curved bilayers of lecithin vesicles obtained by ultrasonic irradiation. This result strongly supports the idea that curvature is a prime factor in determining proton NMR linewidths, probably through a disruptive effect of curvature on the molecular packing in phospholipid bilayers.

Injection of LiC1 to rats (3.0 mmole/kg/day) caused a marked increase in water intake. The polydipsic effect was maximal after 8 – 10 days of treatment and then gradually declined. This reduction in polydipsia was accompanied by a decrease in Li + content of plasma, red blood cells, liver, spleen, kidney and brain. Furthermore, the ratio of tissue to plasma lithium concentration (lithium index) declined in all tissues examined. The decrease in polydipsia was abolished by increasing the dose of LiC1 by 50%. These results suggest that tolerance to the polydipsic effect of lithium develops in the rat during chronic treatment with LiC1 as a result of a reduction in the cells capacity to accumulate lithium.

Mixed dispersions of egg phosphatidylcholine (PC) and the bile salt sodium deoxycholate (DOC) were prepared by various methods, and their turbidities and proton magnetic resonance spectra were studied as a function of time. The spectra of dispersions prepared by dissolving both components in a common organic solvent and replacing the organic solvent by water did not change with time, indicating that the mixed aggregates formed represent "a state of equilibrium". In the 1H NMR spectra of these mixed aggregates, only signals from small mixed micellar structures were narrow enough to be observed. The dependence of the NMR line widths on the molar ratio of DOC to PC (R) is interpreted in terms of a model for the PC--DOC mixed micelles, according to which PC is arranged as a curved bilayer, the curvature of which increases with increasing R. Upon mixing PC with aqueous solutions of DOC, we found that the mixed aggregates formed are slowly reorganized and ultimately reach the same state of equilibrium. This reorganization was found to be a pseudo-first-order process, the rate constant of which depends linearly upon the detergent concentration. This process involves saturation of the outer bilayers of the multilamellar PC by detergent, followed by transformation of these bilayers into mixed micelles. It is concluded that the solubilization occurs through consecutive "peeling off" of lecithin bilayers.