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Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIV Envelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization
No full textAs a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIV lineage express phylogenetically and antigenically distinct envelope glycoproteins. Thus, HIV-1 Env-specific antibodies do not typically cross-react with the Env proteins of SIV isolates. Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIV infectivity. Amino acid substitutions in the V2 loop of SIV239 corresponding to the epitope for PGT145 in HIV-1 Env modulate sensitivity to this antibody. Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization. These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers. To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIV Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization. IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity. This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIV Env and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization
Postcolonial Filiations
No full textThis article examines the structural features and ideological paradigms associated with the genre of filiation narrative by expanding the traditional body of works examined under this lens to a transnational corpus that includes Postcolonial Francophone texts. By using concepts such as di-genèse or dual legacy that characterizes the colonial condition and paracolonialism, which accounts for recent phenomena of relying on colonial representations and the postcolonial context (history, geography, culture) to find new sources of inspiration for Western or “white” writers, the article delves into the limits and contradictions of the genre of filiation narrative and contends that it should be envisioned as an anti‐genealogical genre
Higher smoking prevalence among United States adults with co-occurring affective and drug use diagnoses
No full textIntroduction: Individuals with drug use disorders or affective disorders have higher cigarette smoking prevalence and smoking intensity and are less likely to quit than the general population. We sought to estimate the prevalence of cigarette smoking by drug use and psychiatric diagnoses and to explore to what extent a co-occurring diagnosis was associated with current smoking. Methods: Data were derived from the most recent National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III, 2012–2013; n = 36,309). Cigarette smoking status was examined among those with any past-year or lifetime drug use disorders (i.e., alcohol, cannabis, opioid, cocaine) or affective disorders (i.e., mood, anxiety). Diagnoses were assessed using the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-5). Results: Adjusting for sociodemographic characteristics, those with drug use disorders (past-year AOR = 3.3, 95% CI: 3.0, 3.6; lifetime AOR = 3.2, 95% CI: 3.0, 3.5) and those with affective disorders (past-year AOR = 1.7; 95%CI: 1.5, 1.8, lifetime AOR = 1.3, 95% CI: 1.2; 1.4), had higher odds of current cigarette smoking compared to individuals with no diagnosis. The odds of current cigarette smoking was significantly higher in individuals with both drug use disorders and affective disorders compared to those with either a drug use or affective disorder or no disorder (past-year AOR = 5.1; 95% CI: 4.3, 5.9, lifetime AOR = 4.3; 95% CI: 3.8, 4.7). Conclusions: Approximately 30% of the population had a past-year drug use or affective disorder, 17% of whom report both. The combination of both diagnoses produced a 1.5 to 3-fold higher correlation with smoking than either alone
Reasons for non-medical use of prescription opioids among young adults: Role of educational status
No full textNon-medical use of prescription opioids (NMUPO) and related overdoses are disproportionately elevated among young adults. Efforts to understand the underlying reasons for NMUPO are critical for developing more effective prevention and intervention strategies for this group. Given the robust literature on the association between educational status and substance abuse risk, we examined the reasons for NMUPO through the lens of educational attainment among young adults. Data from the 2016 National Survey on Drug Use and Health came from an unweighted sample of 941 young adults aged 18–25 years who reported past-year NMUPO. Self-reported reasons for most recent NMUPO were compared by educational status. The most commonly-endorsed reasons for past-year NMUPO was physical pain relief (47.6%), followed by feel good/get high (19.8%), relax/relieve tension (13.2%) and experiment/see what it feels like (6.8%). Reasons for NMUPO did not differ as a function educational status (p = 0.17). These findings suggest that efforts to prevent and address opioid misuse among young adults should focus on understanding and improving pain management in this vulnerable population
Data Correction of Intensity Modulated Small Angle Scattering
No full textTo investigate long length scale structures using neutron scattering, real space techniques have shown certain advantages over the conventional methods working in reciprocal space. As one of the real space measurement techniques, spin echo modulated small angle neutron scattering (SEMSANS) has attracted attention, due to its relaxed constraints on sample environment and the possibility to combine SEMSANS and a conventional small angle neutron scattering instrument. In this report, we present the first implementation of SEMSANS at a pulsed neutron source and discuss important corrections to the data due to the sample absorption. These corrections allow measurements made with different neutron wavelengths and SEMSANS configurations to be overlaid and give confidence that the measurements provide an accurate representation of the density correlations in the sample
Reply to Hanlon: Transitions in science careers
No full textWe thank Hanlon for his comments on our paper and appreciate his summary of our findings (1). We recognize the concerns raised regarding both research and non-research roles in science. For example, the National Science Foundation reports various estimates of the science labor force: about 6 million in “science and engineering [S&E] occupations,” about 12 million in non-S&E occupations closely or somewhat related to their S&E degree, about 17 million whose highest degree is in S&E, and about 23 million with at least 1 S&E degree (2)
A New Generation of Cool White Dwarf Atmosphere Models. III. WD J2356-209: Accretion of a Planetesimal with an Unusual Composition
No full textWD J2356−209 is a cool metal-polluted white dwarf whose visible spectrum is dominated by a strong and broad sodium feature. Although discovered nearly two decades ago, no detailed and realistic analysis of this star had yet been realized. In the absence of atmosphere models taking into account the nonideal high-density effects arising at the photosphere of WD J2356−209, the origin of its unique spectrum had remained nebulous. We use the cool white dwarf atmosphere code presented in the first paper of this series to finally reveal the secrets of this peculiar object and details about the planetesimal that polluted its atmosphere. Thanks to the improved input physics of our models, we find a solution that is in excellent agreement with the photometric observations and the visible spectrum. Our solution reveals that the photosphere of WD J2356−209 has a number density ratio of log Na/Ca=1.0±0.2, which is the highest ever found in a white dwarf. Since we do not know how long ago the accretion episode stopped (if it has), we cannot precisely determine the composition nor the mass of the accreted planetesimal. Nevertheless, all scenarios considered indicate that its composition is incompatible with that of chondrite-like material and that its mass was at least 10g
The open diffusion data derivatives, brain data upcycling via integrated publishing of derivatives and reproducible open cloud services
No full textWe describe the Open Diffusion Data Derivatives (O3D) repository: an integrated collection of preserved brain data derivatives and processing pipelines, published together using a single digital-object-identifier. The data derivatives were generated using modern diffusion-weighted magnetic resonance imaging data (dMRI) with diverse properties of resolution and signal-to-noise ratio. In addition to the data, we publish all processing pipelines (also referred to as open cloud services). The pipelines utilize modern methods for neuroimaging data processing (diffusion-signal modelling, fiber tracking, tractography evaluation, white matter segmentation, and structural connectome construction). The O3D open services can allow cognitive and clinical neuroscientists to run the connectome mapping algorithms on new, user-uploaded, data. Open source code implementing all O3D services is also provided to allow computational and computer scientists to reuse and extend the processing methods. Publishing both data-derivatives and integrated processing pipeline promotes practices for scientific reproducibility and data upcycling by providing open access to the research assets for utilization by multiple scientific communities
Leukoaraiosis Is Associated With a Decline in Language Abilities in Chronic Aphasia
No full textBackground. A fraction of stroke survivors with chronic aphasia experience declines in language abilities over time, but the reason for this remains unclear. Objective. To evaluate the effect of leukoaraiosis on baseline aphasia severity and long-term changes in aphasia severity. This study directly compares the predictive capacity of leukoaraiosis severity to that of lesion damage, a factor known to account for a substantial proportion of variance in the degree of language impairment and recovery. Methods. Using a longitudinal database of behavioral and neuroimaging data from 35 individuals in the chronic stage of recovery after a single-event left-hemisphere stroke (9 females, mean stroke age = 55.8 ± 9.1 years, mean months poststroke at initial evaluation = 36.3 ± 40.8), we examined 2 lines of inquiry: (1) to what extent does leukoaraiosis severity at initial evaluation predict aphasia severity and (2) to what extent does leukoaraiosis severity at initial evaluation predict longitudinal change in aphasia severity. Participants underwent high-resolution magnetic resonance imaging for the purpose of lesion volume analysis and leukoaraiosis severity rating. Biographical information was also considered. Results. Lesion volume and time poststroke at initial assessment best predicted initial aphasia severity (adjusted R = 0.37). Leukoaraiosis severity and initial aphasia severity significantly predicted decline in language abilities at follow-up, accounting for approximately one-third of the variance (adjusted R = 0.33). More severe leukoaraiosis was associated with a 4.3 odds increase of decline. Conclusions. Leukoaraiosis is a significant risk factor for declining language abilities in aphasia and should be considered for better identification of individuals at risk for long-term decline, which can guide clinical decision making
Simulating secondary organic aerosol in a regional air quality model using the statistical oxidation model - Part 3: Assessing the influence of semi-volatile and intermediate-volatility organic compounds and NO
No full textSemi-volatile and intermediate-volatility organic compounds (SVOCs and IVOCs) from anthropogenic sources are likely to be important precursors of secondary organic aerosol (SOA) in urban airsheds, yet their treatment in most models is based on limited and obsolete data or completely missing. Additionally, gas-phase oxidation of organic precursors to form SOA is influenced by the presence of nitric oxide (NO), but this influence is poorly constrained in chemical transport models. In this work, we updated the organic aerosol model in the UCD/CIT (University of California at Davis/California Institute of Technology) chemical transport model to include (i) a semi-volatile and reactive treatment of primary organic aerosol (POA), (ii) emissions and SOA formation from IVOCs, (iii) the NO influence on SOA formation, and (iv) SOA parameterizations for SVOCs and IVOCs that are corrected for vapor wall loss artifacts during chamber experiments. All updates were implemented in the statistical oxidation model (SOM) that simulates the oxidation chemistry, thermodynamics, and gas–particle partitioning of organic aerosol (OA). Model treatment of POA, SVOCs, and IVOCs was based on an interpretation of a comprehensive set of source measurements available up to the year 2016 and resolved broadly by source type. The NO influence on SOA formation was calculated offline based on measured and modeled VOC:NO ratios. Finally, the SOA formation from all organic precursors (including SVOCs and IVOCs) was modeled based on recently derived parameterizations that accounted for vapor wall loss artifacts in chamber experiments. The updated model was used to simulate a 2-week summer episode over southern California at a model resolution of 8 km. When combustion-related POA was treated as semi-volatile, modeled POA mass concentrations were reduced by 15 %–40 % in the urban areas in southern California but were still too high when compared against “hydrocarbon-like organic aerosol” factor measurements made at Riverside, CA, during the Study of Organic Aerosols at Riverside (SOAR-1) campaign of 2005. Treating all POA (except that from marine sources) to be semi-volatile, similar to diesel exhaust POA, resulted in a larger reduction in POA mass concentrations and allowed for a better model–measurement comparison at Riverside, but this scenario is unlikely to be realistic since this assumes that POA from sources such as road and construction dust are semi-volatile too. Model predictions suggested that both SVOCs (evaporated POA vapors) and IVOCs did not contribute as much as other anthropogenic precursors (e.g., alkanes, aromatics) to SOA mass concentrations in the urban areas (< 5 % and < 15 % of the total SOA respectively) as the timescales for SOA production appeared to be shorter than the timescales for transport out of the urban airshed. Comparisons of modeled IVOC concentrations with measurements of anthropogenic SOA precursors in southern California seemed to imply that IVOC emissions were underpredicted in our updated model by a factor of 2. Correcting for the vapor wall loss artifact in chamber experiments enhanced SOA mass concentrations although the enhancement was precursor-dependent as well as NO-dependent. Accounting for the influence of NO using the VOC:NO ratios resulted in better predictions of OA mass concentrations in rural/remote environments but still underpredicted OA mass concentrations in urban environments. The updated model's performance against measurements combined with the results from the sensitivity simulations suggests that the OA mass concentrations in southern California are constrained within a factor of 2. Finally, simulations performed for the year 2035 showed that, despite reductions in VOC and NO emissions in the future, SOA mass concentrations may be higher than in the year 2005, primarily from increased hydroxyl radical (OH) concentrations due to lower ambient NO concentrations