399 research outputs found
When Imagining Yourself in Pain, Visual Perspective Matters : The Neural and Behavioral Correlates of Simulated Sensory Experiences
© 2015 Massachusetts Institute of TechnologyPeer reviewedPublisher PD
Age and Inclusivity in Umm an-Nar Communal Tombs from Southeastern Arabia
Umm an-Nar (2700-2000 BCE) tombs in the United Arab Emirates contained the commingled remains of hundreds of individuals interred across multiple generations. Archaeologists commonly reference tomb demographics as being inclusive of all ages, but this assumption is based on a handful of studies that rarely distinguish age categories beyond “subadult” or “adult.” An undergraduate research training program sought to examine age distributions – and thus inclusivity in tomb membership – in greater detail, with a particular focus on fetal and older adult age categories.
A combination of traditional and novel aging techniques were applied to bones from tombs Unar 1 (U1; MNI = 194) and 2 (U2; MNI = 410) at Shimal. Transition Analysis 3 scores for the femur, humerus, and pubic symphysis revealed older age categories not previously recognized in the region, with means ranging from 40.4-47.8 years, contrasting with an average of 31 years produced by Suchey-Brooks. Measurements identified fetuses and perinates in both tombs using the basilar (U1: 5; U2: 10), petrous (U1 left: 29; U2 right: 33), and distal femur (U1 left: 5; U2 left: 11), some as young as 20-22 fetal weeks. MicroCT scans of suspected fetal humeri (U1: 10; U2: 14) revealed a lack of bioerosion, confirming that stillborn infants were permitted access to tombs. These data substantiate the presence of very young and older adults in both tombs, and demonstrate that despite subsistence and environmental changes tied to increasing social stratification during this period, no age group was separated from the larger community in death.https://jagworks.southalabama.edu/present_yr2/1003/thumbnail.jp
Virus-Free CRISPR CAR T cells induce solid tumor regression
Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy in treating hematologic malignancies and has led to the FDA-approval of three CAR T cell products. However, there has been little success in treating solid tumors, as clinical trials to date have yielded little to no responses and no improvement in survival. Current methods of CAR T cell production typically involve the use of viral vectors which can give rise to complications such as insertional mutagenesis, leading to gene silencing or oncogene activation. In addition, GMP-grade viral vector manufacturing can be expensive with lengthy wait times for new batches. Here we have developed a virus-free strategy in primary T cells that has eliminated the use of viral vectors through the use of CRISPR-Cas9 to precisely edit the chimeric antigen receptor into the TRAC gene1. Our method of virus free production begins through the generation of a double stranded DNA (dsDNA) template produced by polymerase chain reaction (PCR). This template is then combined with a SpCas9-single guide RNA to create a ribonucleoprotein (RNP) complex. Isolated human primary T cells from adult healthy donors are then nucleofected with the RNP and dsDNA template on day 2 of ex vivo expansion. Flow cytometry is then utilized to immunophenotype the cell product and analyze the percent of efficiency of CAR gene transfer. Within the cell product, the editing efficiencies are \u3e95% TCR knockout and 35% CAR+. Transcriptional profiling indicates that the virus-free CART cells have a favorable memory-like phenotype. In addition to our in vitro work, in vivo mice studies with anti-GD2 CART products demonstrate regression of GD2+ solid tumors upon virus-free CART treatment, showing similar potency and survival to viral-produced CAR T cells. The production of virus-free CAR T cells has high potential to enable the rapid and flexible manufacturing of highly defined and highly potent CAR T cell products for the treatment of solid tumors. 1 Mueller, K. et al. CRISPR-mediated insertion of a chimeric antigen receptor produces nonviral T cell products capable of inducing solid tumor regression. bioRxiv preprint doi: https://doi.org/10.1101/2021.08.06.455489 (2021)
Noticing Future Me: Reducing Egocentrism Through Mental Imagery.
People drastically overestimate how often others attend to them or notice their unusual features, a phenomenon termed the spotlight effect Despite the prevalence of this egocentric bias, little is known about how to reduce the tendency to see oneself as the object of others' attention. Here, we tested the hypothesis that a basic property of mental imagery-the visual perspective from which an event is viewed-may alleviate a future-oriented variant of the spotlight effect. The results of three experiments supported this prediction. Experiment 1 revealed a reduction in egocentric spotlighting when participants imagined an event in the far compared with near future. Experiments 2 and 3 demonstrated reduced spotlighting and feelings of embarrassment when participants viewed an impending event from a third-person (vs. first-person) vantage point. Simple changes in one's visual perspective may be sufficient to diminish the illusion of personal salience
Virus-Free CRISPR CAR T cells induce solid tumor regression
Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy in treating hematologic malignancies and has led to the FDA-approval of three CAR T cell products. However, there has been little success in treating solid tumors, as clinical trials to date have yielded little to no responses and no improvement in survival. Current methods of CAR T cell production typically involve the use of viral vectors which can give rise to complications such as insertional mutagenesis, leading to gene silencing or oncogene activation. In addition, GMP-grade viral vector manufacturing can be expensive with lengthy wait times for new batches. Here we have developed a virus-free strategy in primary T cells that has eliminated the use of viral vectors through the use of CRISPR-Cas9 to precisely edit the chimeric antigen receptor into the TRAC gene1. Our method of virus free production begins through the generation of a double stranded DNA (dsDNA) template produced by polymerase chain reaction (PCR). This template is then combined with a SpCas9-single guide RNA to create a ribonucleoprotein (RNP) complex. Isolated human primary T cells from adult healthy donors are then nucleofected with the RNP and dsDNA template on day 2 of ex vivo expansion. Flow cytometry is then utilized to immunophenotype the cell product and analyze the percent of efficiency of CAR gene transfer. Within the cell product, the editing efficiencies are \u3e95% TCR knockout and 35% CAR+. Transcriptional profiling indicates that the virus-free CART cells have a favorable memory-like phenotype. In addition to our in vitro work, in vivo mice studies with anti-GD2 CART products demonstrate regression of GD2+ solid tumors upon virus-free CART treatment, showing similar potency and survival to viral-produced CAR T cells. The production of virus-free CAR T cells has high potential to enable the rapid and flexible manufacturing of highly defined and highly potent CAR T cell products for the treatment of solid tumors.
1 Mueller, K. et al. CRISPR-mediated insertion of a chimeric antigen receptor produces nonviral T cell products capable of inducing solid tumor regression. bioRxiv preprint doi: https://doi.org/10.1101/2021.08.06.455489 (2021)
Turning I into me: Imagining your future self.
A widely endorsed belief is that perceivers imagine their present selves using a different representational format than imagining their future selves (i.e., near future=first-person; distant future=third-person). But is this really the case? Responding to the paucity of work on this topic, here we considered how temporal distance influences the extent to which individuals direct their attention outward or inward during a brief imaginary episode. Using a non-verbal measure of visual perspective taking (i.e., letter-drawing task) our results confirmed the hypothesized relation between temporal distance and conceptions of the self. Whereas simulations of an event in the near future were dominated by a first-person representation of the self, this switched to a third-person depiction when the event was located in the distant future. Critically, this switch in vantage point was restricted to self-related simulations. The theoretical and practical implications of these findings are considered
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
The bed bug, Cimex lectularius, has re-established itself as a ubiquitous
human ectoparasite throughout much of the world during the past two decades.
This global resurgence is likely linked to increased international travel and
commerce in addition to widespread insecticide resistance. Analyses of the C.
lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding
genes provide a comprehensive representation of genes that are linked to
traumatic insemination, a reduced chemosensory repertoire of genes related to
obligate hematophagy, host–symbiont interactions, and several mechanisms of
insecticide resistance. In addition, we document the presence of multiple
putative lateral gene transfer events. Genome sequencing and annotation
establish a solid foundation for future research on mechanisms of insecticide
resistance, human–bed bug and symbiont–bed bug associations, and unique
features of bed bug biology that contribute to the unprecedented success of C.
lectularius as a human ectoparasite
The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems II: A 1 to 20 Micron Spectrum of the Planetary-Mass Companion VHS 1256-1257 b
We present the highest fidelity spectrum to date of a planetary-mass object.
VHS 1256 b is a 20 M widely separated (8\arcsec, a =
150 au), young, planetary-mass companion that shares photometric colors and
spectroscopic features with the directly imaged exoplanets HR 8799 c, d, and e.
As an L-to-T transition object, VHS 1256 b exists along the region of the
color-magnitude diagram where substellar atmospheres transition from cloudy to
clear. We observed VHS 1256~b with \textit{JWST}'s NIRSpec IFU and MIRI MRS
modes for coverage from 1 m to 20 m at resolutions of 1,000 -
3,700. Water, methane, carbon monoxide, carbon dioxide, sodium, and potassium
are observed in several portions of the \textit{JWST} spectrum based on
comparisons from template brown dwarf spectra, molecular opacities, and
atmospheric models. The spectral shape of VHS 1256 b is influenced by
disequilibrium chemistry and clouds. We directly detect silicate clouds, the
first such detection reported for a planetary-mass companion.Comment: Accepted ApJL Iterations of spectra reduced by the ERS team are
hosted at this link:
https://github.com/bemiles/JWST_VHS1256b_Reduction/tree/main/reduced_spectr
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