In Life of the Indigenous Mind David Martínez examines the early activism, life, and writings of Vine Deloria Jr. (1933-2005), the most influential indigenous activist and writer of the twentieth ...century and one of the intellectual architects of the Red Power movement. An experienced activist, administrator, and political analyst, Deloria was motivated to activism and writing by his work as executive director of the National Congress of American Indians, and he came to view discourse on tribal self-determination as the most important objective for making a viable future for tribes. In this work of both intellectual and activist history, Martínez assesses the early life and legacy of Deloria's "Red Power Tetralogy," his most powerful and polemical works:Custer Died for Your Sins (1969), We Talk, You Listen (1970), God Is Red (1973), and Behind the Trail of Broken Treaties (1974). Deloria's gift for combining sharp political analysis with a cutting sense of humor rattled his adversaries as much as it delighted his growing readership. Life of the Indigenous Mind reveals how Deloria's writings addressed Indians and non-Indians alike. It was in the spirit of protest that Deloria famously and infamously confronted the tenets of Christianity, the policies of the Bureau of Indian Affairs, and the theories of anthropology. The concept of tribal self-determination that he initiated both overturned the presumptions of the dominant society, including various "Indian experts," and asserted that tribes were entitled to the rights of independent sovereign nations in their relationship with the United States, be it legally, politically, culturally, historically, or religiously.
DNA replication stress can cause chromosomal instability and tumor progression. One key pathway that counteracts replication stress and promotes faithful DNA replication consists of the Fanconi ...anemia (FA) proteins. However, how these proteins limit replication stress remains largely elusive. Here we show that conflicts between replication and transcription activate the FA pathway. Inhibition of transcription or enzymatic degradation of transcription-associated R-loops (DNA:RNA hybrids) suppresses replication fork arrest and DNA damage occurring in the absence of a functional FA pathway. Furthermore, we show that simple aldehydes, known to cause leukemia in FA-deficient mice, induce DNA:RNA hybrids in FA-depleted cells. Finally, we demonstrate that the molecular mechanism by which the FA pathway limits R-loop accumulation requires FANCM translocase activity. Failure to activate a response to physiologically occurring DNA:RNA hybrids may critically contribute to the heightened cancer predisposition and bone marrow failure of individuals with mutated FA proteins.
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•Replication and transcription collisions cause genome instability in FA•A functional FA pathway protects cells from unscheduled accumulation of R-loops•Transcription inhibition or R-loop removal restores normal replication in FA cells•FANCM resolves R-loops via its translocase activity
Schwab et al. show that the FA pathway prevents DNA lesions caused by conflicts between replication and transcription and by transcription-associated DNA:RNA hybrids (R-loops). FA proteins can stabilize stalled replication forks, and FANCM resolves R-loops via its translocase activity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to ...explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.
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•A SARS-CoV-2 infectious cDNA clone and reporter viruses are generated•SARS-CoV-2 and SARS-CoV neutralization assays show limited cross neutralization•SARS-CoV-2 shows a gradient infectivity from the proximal to distal respiratory tract•Ciliated airway cells and AT-2 cells are primary targets for SARS-CoV-2 infection
Hou et al. present a reverse genetics system for SARS-CoV-2, which is then used to make reporter viruses to quantify the ability of patient sera and antibodies to neutralize infectious virus and to examine viral tropism along the human respiratory tract.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Digital Light Processing (DLP) allows the fast realization of 3D objects with high spatial resolution. However, DLP is limited to transparent resins, and therefore not well suited for printing ...electrically conductive materials. Manufacturing conductive materials will significantly broaden the spectrum of applications of the DLP technology. But conductive metals or carbon‐based fillers absorb and scatter light; inhibiting thereby photopolymerization, and lowering resolution. In this study, UV transparent liquid crystal graphene oxide (GO) is used as precursor for generating in situ conductive particles. The GO materials are added to a photopolymerizable resin via an original solvent exchange process. By contrast to earlier contributions, the absence of drying during the all process allows the GO material to be transferred as monolayers to limit UV scattering. The absence of UV scattering and absorption allows for fast and high‐resolution 3D printing. The chosen resin sustain high temperature to enable an in situ efficient thermal reduction of GO into reduced graphene oxide (rGO) that is electrically conductive. The rGO particles form percolated networks with conductivities up to 1.2 × 10−2 S m−1. The present method appears therefore as a way to reconcile the DLP technology with the manufacturing of 3D electrically conductive objects.
A method to 3D print conductive objects by Digital Light Processing is reported. Transparent graphene oxide (GO)‐resin materials are 3D printed. Transparency allows high quality and fast printing. GO monolayers are thermally reduced in situ to form a conductive network of reduced graphene oxide.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The Ad26.COV2.S vaccine
has demonstrated clinical efficacy against symptomatic COVID-19, including against the B.1.351 variant that is partially resistant to neutralizing antibodies
. However, the ...immunogenicity of this vaccine in humans against SARS-CoV-2 variants of concern remains unclear. Here we report humoral and cellular immune responses from 20 Ad26.COV2.S vaccinated individuals from the COV1001 phase I-IIa clinical trial
against the original SARS-CoV-2 strain WA1/2020 as well as against the B.1.1.7, CAL.20C, P.1 and B.1.351 variants of concern. Ad26.COV2.S induced median pseudovirus neutralizing antibody titres that were 5.0-fold and 3.3-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020 on day 71 after vaccination. Median binding antibody titres were 2.9-fold and 2.7-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020. Antibody-dependent cellular phagocytosis, complement deposition and natural killer cell activation responses were largely preserved against the B.1.351 variant. CD8 and CD4 T cell responses, including central and effector memory responses, were comparable among the WA1/2020, B.1.1.7, B.1.351, P.1 and CAL.20C variants. These data show that neutralizing antibody responses induced by Ad26.COV2.S were reduced against the B.1.351 and P.1 variants, but functional non-neutralizing antibody responses and T cell responses were largely preserved against SARS-CoV-2 variants. These findings have implications for vaccine protection against SARS-CoV-2 variants of concern.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
B-cell and T-cell responses were measured to assess the stability and duration of vaccine-induced immunity. Responses to BNT162b2 and mRNA-1273 peaked early and declined over 6 to 8 months. The ...response to Ad26.CoV2.S reached a lower peak but continued without evidence of notable decline for 8 months. Response levels correlating with protection have not yet been defined.
CoA (coenzyme A) is an essential cofactor in all living organisms. CoA and its thioester derivatives acetyl-CoA, malonyl-CoA, HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) etc. participate in diverse ...anabolic and catabolic pathways, allosteric regulatory interactions and the regulation of gene expression. The biosynthesis of CoA requires pantothenic acid, cysteine and ATP, and involves five enzymatic steps that are highly conserved from prokaryotes to eukaryotes. The intracellular levels of CoA and its derivatives change in response to extracellular stimuli, stresses and metabolites, and in human pathologies, such as cancer, metabolic disorders and neurodegeneration. In the present mini-review, we describe the current understanding of the CoA biosynthetic pathway, provide a detailed overview on expression and subcellular localization of enzymes implicated in CoA biosynthesis, their regulation and the potential to form multi-enzyme complexes for efficient and highly co-ordinated biosynthetic process.
Auditory prediction error responses elicited by surprising sounds can be reliably recorded with musical stimuli that are more complex and realistic than those typically employed in EEG or MEG oddball ...paradigms. However, these responses are reduced as the predictive uncertainty of the stimuli increases. In this study, we investigate whether this effect is modulated by musical expertise. Magnetic mismatch negativity (MMNm) responses were recorded from 26 musicians and 24 non‐musicians while they listened to low‐ and high‐uncertainty melodic sequences in a musical multi‐feature paradigm that included pitch, slide, intensity and timbre deviants. When compared to non‐musicians, musically trained participants had significantly larger pitch and slide MMNm responses. However, both groups showed comparable reductions in pitch and slide MMNm amplitudes in the high‐uncertainty condition compared with the low‐uncertainty condition. In a separate, behavioural deviance detection experiment, musicians were more accurate and confident about their responses than non‐musicians, but deviance detection in both groups was similarly affected by the uncertainty of the melodies. In both experiments, the interaction between uncertainty and expertise was not significant, suggesting that the effect is comparable in both groups. Consequently, our results replicate the modulatory effect of predictive uncertainty on prediction error; show that it is present across different types of listeners; and suggest that expertise‐related and stimulus‐driven modulations of predictive precision are dissociable and independent.
Predictive uncertainty in music listening reduces neural (magnetic mismatch negativity) responses to unexpected sounds in the pitch dimension (i.e. pitch and slide deviants). While musicians tend to have overall larger responses to these deviants, the effect of uncertainty is similar in both groups. These results are corroborated in a behavioural task of pitch deviance detection. Our findings indicate that the long‐term, expertise‐driven increase in the precision of internal predictive models is dissociable and independent from the short‐term, stimulus‐driven increase in the uncertainty of musical predictions.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no ...approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). Antibody combinations were effective for prevention and in therapy when administered early. However, in vitro antibody neutralization potency did not uniformly correlate with in vivo protection, and some hu-mAbs were more protective in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors contributes to optimal protection against SARS-CoV-2 MA. The data indicate that intact effector function can affect hu-mAb protective activity and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.
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