162 research outputs found
Personal Narrative as Shaping the Activist Identity of Religious Women in Israel
This article is based on the life stories of 14 religious activist women in Israel. It aims to understand the extent to which these women’s stories and their childhood and maturation experiences shaped their activist identity. In this qualitative, critical-feminist study, the women activists’ life stories were examined using semi-structured interviews. The findings indicate that personal or social events perceived as significant in the women’s lives as children and adolescents acted as catalysts for activism. These events were central to their personal narratives and became embedded in the women’s activist identity, as they came to perceive activism as the most “natural” response to life challenges. Specifically, two types of events were identified: events in the individual-family-community sphere and events in the public-national sphere. They affected the interviewees and led them to act, whether out of antagonism and anger at a perceived injustice, or out of a sense of power and constructive thought. This study contributes to the literature by highlighting the new and unique phenomenon of religious women who, despite being educated to accept and comply with the conventions of a patriarchal society, choose to make their voice heard and lead sociocultural changes in public spaces. The findings emphasize the personal-political nexus and provide insight into the activists’ motives for fighting for their values and for committing to long-term activity in the public sphere—despite considerable personal costs
“I’m Different from You but Very Much Like You”: Religious Women Activists and their Father Figures
This study examined activist women in religious society in Israel in order to gain in-depth insights into their lived experience and coping strategies in advocating for change in their society. The article is based on thematic analysis of semi-structured interviews with fourteen such women. Contrary to the expectation that there would be a dominant mother figure influencing the activists’ lives, the findings show that the influence of mothers was marginal and even an impeding factor, while father figures were the most significant in these women’s childhood and development into activists. All religious activists perceived their fathers as highly influential, in three contexts: the father as a pioneer, the father as an extraordinary figure, and a strong attachment to the father. Based on these findings, we believe it is important to involve and integrate men in programs that act to promote and empower religious women in Israeli society on both the political and occupational level
MR imaging–derived oxygen-hemoglobin dissociation curves and fetal-placental oxygen-hemoglobin affinities
PURPOSE: To generate magnetic resonance (MR) imaging–derived, oxygen-hemoglobin dissociation curves and to map fetal-placental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level–dependent (BOLD) T2* and oxygen-weighted T1 contrast mechanisms under different respiration challenges. MATERIALS AND METHODS: All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.4 T on embryonic days 14.5 (eight dams and 58 fetuses; imprinting control region ICR strain) and 17.5 (21 dams and 158 fetuses) under respiration challenges ranging from hyperoxia to hypoxia (10 levels of oxygenation, 100%–10%; total imaging time, 100 minutes). A shorter protocol with normoxia to hyperoxia was also performed (five levels of oxygenation, 20%–100%; total imaging time, 60 minutes). Fast spin-echo anatomic images were obtained, followed by sequential acquisition of three-dimensional gradient-echo T2*- and T1-weighted images. Automated registration was applied to align regions of interest of the entire placenta, fetal liver, and maternal liver. Results were compared by using a two-tailed unpaired Student t test. R1 and R2* values were derived for each tissue. MR imaging–based oxygen-hemoglobin dissociation curves were constructed by nonlinear least square fitting of 1 minus the change in R2*divided by R2*at baseline as a function of R1 to a sigmoid-shaped curve. The apparent P50 (oxygen tension at which hemoglobin is 50% saturated) value was derived from the curves, calculated as the R1 scaled value (x) at which the change in R2* divided by R2*at baseline scaled (y) equals 0.5. RESULTS: The apparent P50 values were significantly lower in fetal liver than in maternal liver for both gestation stages (day 14.5: 21% ± 5 [P = .04] and day 17.5: 41% ± 7 [P < .0001]). The placenta showed a reduction of 18% ± 4 in mean apparent P50 values from day 14.5 to day 17.5 (P = .003). Reproduction of the MR imaging–based oxygen-hemoglobin dissociation curves with a shorter protocol that excluded the hypoxic periods was demonstrated. CONCLUSION: MR imaging–based oxygen-hemoglobin dissociation curves and oxygen-hemoglobin affinity information were derived for pregnant mice by using 9.4-T MR imaging, which suggests a potential to overcome the need for direct sampling of fetal or maternal blood. Online supplemental material is available for this article
Regulation of CLL survival by hypoxia-inducible factor and its target genes
AbstractChronic lymphocytic leukemia (CLL), the most common adult leukemia in the Western world, is characterized by the progressive accumulation of small mature CD5+B lymphocytes in the peripheral blood, lymphoid organs, and bone marrow (BM). The main feature of the disease is decreased apoptosis, resulting in the pathologic accumulation of these malignant cells. Appropriate cellular responses to changes in oxygen tension during normal development or pathological processes, such as cardiovascular disease and cancer, are ultimately regulated by the transcription factor, hypoxia-inducible factor (HIF). Unlike their normal counterparts, CLL cells express HIF-1α even under normoxia. In addition, overexpression of HIF-1α has been observed in leukemic cells in BM specimens from CLL patients. The HIF transcription factor has been implicated in controlling the expression of a wide variety of genes implicated in apoptosis, angiogenesis, invasion, and metastasis. This review describes pathways regulating CLL survival with a focus on HIF-1α and its target genes, MIF and Midkine (MK), and the potential cross-talk between these factors
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Ultralow-threshold, continuous-wave upconverting lasing from subwavelength plasmons.
Miniaturized lasers are an emerging platform for generating coherent light for quantum photonics, in vivo cellular imaging, solid-state lighting and fast three-dimensional sensing in smartphones1-3. Continuous-wave lasing at room temperature is critical for integration with opto-electronic devices and optimal modulation of optical interactions4,5. Plasmonic nanocavities integrated with gain can generate coherent light at subwavelength scales6-9, beyond the diffraction limit that constrains mode volumes in dielectric cavities such as semiconducting nanowires10,11. However, insufficient gain with respect to losses and thermal instabilities in nanocavities has limited all nanoscale lasers to pulsed pump sources and/or low-temperature operation6-9,12-15. Here, we show continuous-wave upconverting lasing at room temperature with record-low thresholds and high photostability from subwavelength plasmons. We achieve selective, single-mode lasing from Yb3+/Er3+-co-doped upconverting nanoparticles conformally coated on Ag nanopillar arrays that support a single, sharp lattice plasmon cavity mode and greater than wavelength λ/20 field confinement in the vertical dimension. The intense electromagnetic near-fields localized in the vicinity of the nanopillars result in a threshold of 70 W cm-2, orders of magnitude lower than other small lasers. Our plasmon-nanoarray upconverting lasers provide directional, ultra-stable output at visible frequencies under near-infrared pumping, even after six hours of constant operation, which offers prospects in previously unrealizable applications of coherent nanoscale light
Yersinia pestis Endowed with Increased Cytotoxicity Is Avirulent in a Bubonic Plague Model and Induces Rapid Protection against Pneumonic Plague
An important virulence strategy evolved by bacterial pathogens to overcome host defenses is the modulation of host cell death. Previous observations have indicated that Yersinia pestis, the causative agent of plague disease, exhibits restricted capacity to induce cell death in macrophages due to ineffective translocation of the type III secretion effector YopJ, as opposed to the readily translocated YopP, the YopJ homologue of the enteropathogen Yersinia enterocolitica O∶8. This led us to suggest that reduced cytotoxic potency may allow pathogen propagation within a shielded niche, leading to increased virulence. To test the relationship between cytotoxic potential and virulence, we replaced Y. pestis YopJ with YopP. The YopP-expressing Y. pestis strain exhibited high cytotoxic activity against macrophages in vitro. Following subcutaneous infection, this strain had reduced ability to colonize internal organs, was unable to induce septicemia and exhibited at least a 107-fold reduction in virulence. Yet, upon intravenous or intranasal infection, it was still as virulent as the wild-type strain. The subcutaneous administration of the cytotoxic Y. pestis strain appears to activate a rapid and potent systemic, CTL-independent, immunoprotective response, allowing the organism to overcome simultaneous coinfection with 10,000 LD50 of virulent Y. pestis. Moreover, three days after subcutaneous administration of this strain, animals were also protected against septicemic or primary pneumonic plague. Our findings indicate that an inverse relationship exists between the cytotoxic potential of Y. pestis and its virulence following subcutaneous infection. This appears to be associated with the ability of the engineered cytotoxic Y. pestis strain to induce very rapid, effective and long-lasting protection against bubonic and pneumonic plague. These observations have novel implications for the development of vaccines/therapies against Y. pestis and shed new light on the virulence strategies of Y. pestis in nature
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Endogenous siRNAs promote proteostasis and longevity in germline-less Caenorhabditis elegans.
How lifespan and the rate of aging are set is a key problem in biology. Small RNAs are conserved molecules that impact diverse biological processes through the control of gene expression. However, in contrast to miRNAs, the role of endo-siRNAs in aging remains unexplored. Here, by combining deep sequencing and genomic and genetic approaches in Caenorhabditis elegans, we reveal an unprecedented role for endo-siRNA molecules in the maintenance of proteostasis and lifespan extension in germline-less animals. Furthermore, we identify an endo-siRNA-regulated tyrosine phosphatase, which limits the longevity of germline-less animals by restricting the activity of the heat shock transcription factor HSF-1. Altogether, our findings point to endo-siRNAs as a link between germline removal and the HSF-1 proteostasis and longevity-promoting somatic pathway. This establishes a role for endo siRNAs in the aging process and identifies downstream genes and physiological processes that are regulated by the endo siRNAs to affect longevity
Giant nonlinear optical responses from photon avalanching nanoparticles
Avalanche phenomena leverage steeply nonlinear dynamics to generate
disproportionately high responses from small perturbations and are found in a
multitude of events and materials, enabling technologies including optical
phase-conjugate imaging, infrared quantum counting, and efficient upconverted
lasing. However, the photon avalanching (PA) mechanism underlying these optical
innovations has been observed only in bulk materials and aggregates, and
typically at cryogenic temperatures, limiting its utility and impact. Here, we
report the realization of PA at room temperature in single
nanostructures--small, Tm-doped upconverting nanocrystals--and demonstrate
their use in superresolution imaging at near-infrared (NIR) wavelengths within
spectral windows of maximal biological transparency. Avalanching nanoparticles
(ANPs) can be pumped by continuous-wave or pulsed lasers and exhibit all of the
defining features of PA. These hallmarks include excitation power thresholds,
long rise time at threshold, and a dominant excited-state absorption that is
>13,000x larger than ground-state absorption. Beyond the avalanching threshold,
ANP emission scales nonlinearly with the 26th power of pump intensity. This
enables the realization of photon-avalanche single-beam superresolution imaging
(PASSI), achieving sub-70 nm spatial resolution using only simple scanning
confocal microscopy and before any computational analysis. Pairing their steep
nonlinearity with existing superresolution techniques and computational
methods, ANPs allow for imaging with higher resolution and at ca. 100-fold
lower excitation intensities than is possible with other probes. The low PA
threshold and exceptional photostability of ANPs also suggest their utility in
a diverse array of applications including sub-wavelength bioimaging, IR
detection, temperature and pressure transduction, neuromorphic computing, and
quantum optics.Comment: 14 pages, 4 figure
Indefinite and Bidirectional Near Infrared Nanocrystal Photoswitching
Materials whose luminescence can be switched by optical stimulation drive
technologies ranging from superresolution imaging1-4, nanophotonics5, and
optical data storage6-8, to targeted pharmacology, optogenetics, and chemical
reactivity9. These photoswitchable probes, including organic fluorophores and
proteins, are prone to photodegradation, and often require phototoxic doses of
ultraviolet (UV) or visible light. Colloidal inorganic nanoparticles have
significant stability advantages over existing photoswitchable materials, but
the ability to switch emission bidirectionally, particularly with NIR light,
has not been reported with nanoparticles. Here, we present 2-way, near-infrared
(NIR) photoswitching of avalanching nanoparticles (ANPs), showing full optical
control of upconverted emission using phototriggers in the NIR-I and NIR-II
spectral regions useful for subsurface imaging. Employing single-step
photodarkening10-13 and photobrightening12,14-18, we demonstrate indefinite
photoswitching of individual nanoparticles (>1000 cycles over 7 h) in ambient
or aqueous conditions without measurable photodegradation. Critical steps of
the photoswitching mechanism are elucidated by modeling and by measuring the
photon avalanche properties of single ANPs in both bright and dark states.
Unlimited, reversible photoswitching of ANPs enables indefinitely rewritable 2D
and 3D multi-level optical patterning of ANPs, as well as optical nanoscopy
with sub-{\AA} localization superresolution that allows us to distinguish
individual ANPs within tightly packed clusters.Comment: 15 pages, 5 figure
Molecular imaging of cell death in vivo by a novel small molecule probe
Apoptosis has a role in many medical disorders, therefore assessment of apoptosis in vivo can be highly useful for diagnosis, follow-up and evaluation of treatment efficacy. ApoSense is a novel technology, comprising low molecular-weight probes, specifically designed for imaging of cell death in vivo. In the current study we present targeting and imaging of cell death both in vitro and in vivo, utilizing NST-732, a member of the ApoSense family, comprising a fluorophore and a fluorine atom, for both fluorescent and future positron emission tomography (PET) studies using an 18F label, respectively. In vitro, NST-732 manifested selective and rapid accumulation within various cell types undergoing apoptosis. Its uptake was blocked by caspase inhibition, and occurred from the early stages of the apoptotic process, in parallel to binding of Annexin-V, caspase activation and alterations in mitochondrial membrane potential. In vivo, NST-732 manifested selective uptake into cells undergoing cell-death in several clinically-relevant models in rodents: (i) Cell-death induced in lymphoma by irradiation; (ii) Renal ischemia/reperfusion; (iii) Cerebral stroke. Uptake of NST-732 was well-correlated with histopathological assessment of cell-death. NST-732 therefore represents a novel class of small-molecule detectors of apoptosis, with potential useful applications in imaging of the cell death process both in vitro and in vivo
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