Differential Test Performance in the American Educational System: The Impact of Race and Gender

Contrary to Herrnstein and Murray (1994) who claim that racial groups have different cognitive endowments and that these best explain differential test score achievements, our regression analyses document that there is less improvement in test scores per year of education for African-Americans and women. That is, the observed group test score differences do not appear to be due to racial cognitive differences but rather to other factors associated with group-linked experiences in the educational system. We found that 666 of the subjects in the Herrnstein-Murray database had actual IQ scores derived from school records. Using these as independent controls for IQ, we document that each of the test components that were the basis of the Herrnstein-Murray IQ scores was significantly associated with education level (p\u3c .001). Consequently, their IQ score appears to be an education-related measure rather than an IQ test, and thus challenges the validity of their analysis

Dynamics and dispensability of variant-specific histone H1 Lys-26/Ser-27 and Thr-165 post-translational modifications

Jean-Michel Terme et al.In mammals, the linker histone H1, involved in DNA packaging into chromatin, is represented by a family of variants. H1 tails undergo post-translational modifications (PTMs) that can be detected by mass spectrometry. We developed antibodies to analyze several of these as yet unexplored PTMs including the combination of H1.4 K26 acetylation or trimethylation and S27 phosphorylation. H1.2-T165 phosphorylation was detected at S and G2/M phases of the cell cycle and was dispensable for chromatin binding and cell proliferation; while the H1.4-K26 residue was essential for proper cell cycle progression. We conclude that histone H1 PTMs are dynamic over the cell cycle and that the recognition of modified lysines may be affected by phosphorylation of adjacent residues. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.This work was supported by the Spanish Ministry of Science and Innovation (MICINN) and European Regional Development Fund (Grant BFU2011-23057 to A.J., and Grant BFU2008-00460 to P.S.), and by the Regional Government of Catalonia (Generalitat de Catalunya; Grant 2009-SGR-1222 to A.J.). J.-M.T. received a JAE-Doc contract from the Spanish National Research Council (CSIC)-MICINN; R.M. a TA contract from CSIC-MICINN; and L.M.-A. an FPU predoctoral fellowship from MICINNPeer Reviewe

Dynamics and dispensability of variant-specific histone H1 Lys-26/Ser-27 and Thr-165 post-translational modifications

Jean-Michel Terme et al.In mammals, the linker histone H1, involved in DNA packaging into chromatin, is represented by a family of variants. H1 tails undergo post-translational modifications (PTMs) that can be detected by mass spectrometry. We developed antibodies to analyze several of these as yet unexplored PTMs including the combination of H1.4 K26 acetylation or trimethylation and S27 phosphorylation. H1.2-T165 phosphorylation was detected at S and G2/M phases of the cell cycle and was dispensable for chromatin binding and cell proliferation; while the H1.4-K26 residue was essential for proper cell cycle progression. We conclude that histone H1 PTMs are dynamic over the cell cycle and that the recognition of modified lysines may be affected by phosphorylation of adjacent residues. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.This work was supported by the Spanish Ministry of Science and Innovation (MICINN) and European Regional Development Fund (Grant BFU2011-23057 to A.J., and Grant BFU2008-00460 to P.S.), and by the Regional Government of Catalonia (Generalitat de Catalunya; Grant 2009-SGR-1222 to A.J.). J.-M.T. received a JAE-Doc contract from the Spanish National Research Council (CSIC)-MICINN; R.M. a TA contract from CSIC-MICINN; and L.M.-A. an FPU predoctoral fellowship from MICINNPeer Reviewe

Engineering thermosensitive liposome-nanoparticle hybrids loaded with doxorubicin for heat-triggered drug release

The engineering of responsive multifunctional delivery systems that combine therapeutic and diagnostic (theranostic) capabilities holds great promise and interest. We describe the design of thermosensitive liposome-nanoparticle (NP) hybrids that can modulate drug release in response to external heating stimulus. These hybrid systems were successfully engineered by the incorporation of gold, silver, and iron oxide NPs into the lipid bilayer of lysolipid-containing thermosensitive liposomes (LTSL). Structural characterization of LTSL-NP hybrids using cryo-EM and AFM revealed the incorporation of metallic NPs into the lipid membranes without compromising doxorubicin loading and retention capability. The presence of metallic NPs in the lipid bilayer reinforced bilayer retention and offered a nanoparticle concentration-dependent modulation of drug release in response to external heating. In conclusion, LTSL-NP hybrids represent a promising versatile platform based on LTSL liposomes that could further utilize the properties of the embedded NPs for multifunctional theranostic applications

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Combination of biological screening in a cellular model of viral latency with virtual screening identifies novel compounds that reactivate HIV-1

et al.Although highly active antiretroviral therapy (HAART) has converted HIV into a chronic disease, a reservoir of HIV latently infected resting T cells prevents the eradication of the virus from patients. To achieve eradication, HAART must be combined with drugs that reactivate the dormant viruses. We examined this problem in an established model of HIV postintegration latency by screening a library of small molecules. Initially, we identified eight molecules that reactivated latent HIV. Using them as templates, additional hits were identified by means of similarity-based virtual screening. One of those hits, 8-methoxy-6-methylquinolin-4-ol (MMQO), proved to be useful to reactivate HIV-1 in different cellular models, especially in combination with other known reactivating agents, without causing T-cell activation and with lower toxicity than that of the initial hits. Interestingly, we have established that MMQO produces Jun N-terminal protein kinase (JNK) activation and enhances the T-cell receptor (TCR)/CD3 stimulation of HIV-1 reactivation from latency but inhibits CD3-induced interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α) gene transcription. Moreover, MMQO prevents TCR-induced cell cycle progression and proliferation in primary T cells. The present study documents that the combination of biological screening in a cellular model of viral latency with virtual screening is useful for the identification of novel agents able to reactivate HIV-1. Moreover, we set the bases for a hypothetical therapy to reactivate latent HIV by combining MMQO with physiological or pharmacological TCR/CD3 stimulation.This work was supported by grants from the Fundación para la Investigación y Prevención del SIDA en España (FIPSE; 36602/06 and 360946/10), Fundación Eugenio Rodríguez Pascual, Instituto de Salud Carlos III Fondo de Investigación Sanitaria (PI05/1831), Ministerio de Ciencia e Innovación (MICINN) and FEDER (BFU2008-00359/BMC), and the Generalitat de Catalunya (2009-SGR-1222) to A.J.; grant BIO2008-02329 to J.M.; and grants SAF2010-19292, FIPSE 36710/08, and ISCIII-RETIC RD06/006 to E.M. E.G. was the recipient of a fellowship from the Generalitat de Catalunya and was also supported by intramural resources from the Centre de Regulació Genòmica and Institut de Biologia Molecular de Barcelona-CSIC. J.-M.T. was the recipient of a fellowship from the Fondation pour la Recherche Medicale and a JAE-Doc contract from CSICMICINN.Peer Reviewe

Specificity of human histone H1 subtypes: phenotypic effects of H1 knock-down, genomic distribution and post-translational modifications

Trabajo presentado en el XXXIV Congreso de la Sociedad Española de Bioquímica y Biología Molecular (SEBBM 2011), celebrado en Barcelona, España, del 5 al 8 de septiembre de 2011Peer Reviewe

SWI/SNF regulates half of its targets without the need of ATP-driven nucleosome remodeling by Brahma

Background: Brahma (BRM) is the only catalytic subunit of the SVVI/SNF chromatin-remodeling complex of Drosophila melanogaster. The function of SWI/SNF in transcription has long been attributed to its ability to remodel nucleosomes, which requires the ATPase activity of BRM. However, recent studies have provided evidence for a non-catalytic function of BRM in the transcriptional regulation of a few specific genes. Results: Here we have used RNA-seq and ChIP-seq to identify the BRM target genes in 52 cells, and we have used a catalytically inactive BRM mutant (K804R) that is unable to hydrolyze ATP to investigate the magnitude of the non-catalytic function of BRM in transcription regulation. We show that 49% of the BRM target genes in 52 cells are regulated through mechanisms that do not require BRM to have an ATPase activity. We also show that the catalytic and non-catalytic mechanisms of SVVI/SNF regulation operate on two subsets of genes that differ in promoter architecture and are linked to different biological processes. Conclusions: This study shows that the non-catalytic role of SWI/SNF in transcription regulation is far more prevalent than previously anticipated and that the genes that are regulated by SVVI/SNF through ATPase-dependent and ATPase-independent mechanisms have specialized roles in different cellular and developmental processes

Mapping of six somatic linker histone H1 variants in human breast cancer cells uncovers specific features of H1.2

Seven linker histone H1 variants are present in human somatic cells with distinct prevalence across cell types. Despite being key structural components of chromatin, it is not known whether the different variants have specific roles in the regulation of nuclear processes or are differentially distributed throughout the genome. Using variant-specific antibodies to H1 and hemagglutinin (HA)-tagged recombinant H1 variants expressed in breast cancer cells, we have investigated the distribution of six H1 variants in promoters and genome-wide. H1 is depleted at promoters depending on its transcriptional status and differs between variants. Notably, H1.2 is less abundant than other variants at the transcription start sites of inactive genes, and promoters enriched in H1.2 are different from those enriched in other variants and tend to be repressed. Additionally, H1.2 is enriched at chromosomal domains characterized by low guanine–cytosine (GC) content and is associated with lamina-associated domains. Meanwhile, other variants are associated with higher GC content, CpG islands and gene-rich domains. For instance, H1.0 and H1X are enriched at gene-rich chromosomes, whereas H1.2 is depleted. In short, histone H1 is not uniformly distributed along the genome and there are differences between variants, H1.2 being the one showing the most specific pattern and strongest correlation with low gene expression.Ministerio de Ciencia e Innovació n of Spain (MICINN) and FEDER [BFU2011-23057 to A.J.]; Ministerio de Economía y Competitividad [SAF2012-36199 to N.L.-B.]; Generalitat de Catalunya [2009-SGR-1222 to A.J.]; JAE-Doc contract from CSIC-MICINN (to J.-M.T.); TA contract from CSIC-MICINN (to R.M.); FPU predoctoral fellowship from MICINN (to L.M.-A.). Funding for open access charge: Ministerio de Ciencia e Innovación of Spain (MICINN) and FEDER [BFU2011-23057 to A.J.