Empirical studies on the USA have not reached a consensus on whether its demand is wage- or profit-led, leading many scholars to scrutinize what drives the empirical results. This article tests two ...possible explanations for profit-led results which are related to the presence of overhead labour. To do so, a vector autoregression model is estimated for the USA from 1964 to 2010 and the wage share is split between supervisors/managers and direct workers. The results support the argument that the income redistribution away from workers and towards managers increased the likelihood of profit-led demand and suggest that an increase in the workers' share of income would stimulate the economy. Also, increases in capacity utilization negatively affect the supervisors' share, so that short-run profit-led results may be capturing the cyclical behaviour of the profit share, but the effect becomes positive as time goes by, suggesting a complex determination of functional income distribution, as capacity utilization affects it in ambiguous ways.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), primarily infects cells at mucosal surfaces. Serum neutralizing antibody ...responses are variable and generally low in individuals that suffer mild forms of COVID-19. Although potent immunoglobulin G (IgG) antibodies can neutralize the virus, less is known about secretory antibodies such as IgA that might affect the initial viral spread and transmissibility from the mucosa. Here, we characterize the IgA response to SARS-CoV-2 in a cohort of 149 convalescent individuals after diagnosis with COVID-19. IgA responses in plasma generally correlated with IgG responses. Furthermore, clones of IgM-, IgG-, and IgA-producing B cells were derived from common progenitor cells. Plasma IgA monomers specific to SARS-CoV-2 proteins were demonstrated to be twofold less potent than IgG equivalents. However, IgA dimers, the primary form of antibody in the nasopharynx, were, on average, 15 times more potent than IgA monomers against the same target. Thus, dimeric IgA responses may be particularly valuable for protection against SARS-CoV-2 and for vaccine efficacy.
Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill ...HIV-1–infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4⁺ T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcγ receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1–infected cells.
Monotherapy of HIV-1 infection with single antiretroviral agents is ineffective because error-prone HIV-1 replication leads to the production of drug-resistant viral variants
. Combinations of drugs ...can establish long-term control, however, antiretroviral therapy (ART) requires daily dosing, can cause side effects and does not eradicate the infection
. Although anti-HIV-1 antibodies constitute a potential alternative to ART
, treatment of viremic individuals with a single antibody also results in emergence of resistant viral variants
. Moreover, combinations of first-generation anti-HIV-1 broadly neutralizing antibodies (bNAbs) had little measurable effect on the infection
. Here we report on a phase 1b clinical trial ( NCT02825797 ) in which two potent bNAbs, 3BNC117
and 10-1074
, were administered in combination to seven HIV-1 viremic individuals. Infusions of 30 mg kg
of each of the antibodies were well-tolerated. In the four individuals with dual antibody-sensitive viruses, immunotherapy resulted in an average reduction in HIV-1 viral load of 2.05 log
copies per ml that remained significantly reduced for three months following the first of up to three infusions. In addition, none of these individuals developed resistance to both antibodies. Larger studies will be necessary to confirm the efficacy of antibody combinations in reducing HIV-1 viremia and limiting the emergence of resistant viral variants.
Latent reservoirs of HIV-1-infected cells are refractory to antiretroviral therapies (ART) and remain the major barrier to curing HIV-1. Because latently infected cells are long-lived, ...immunologically invisible, and may undergo homeostatic proliferation, a “shock and kill” approach has been proposed to eradicate this reservoir by combining ART with inducers of viral transcription. However, all attempts to alter the HIV-1 reservoir in vivo have failed to date. Using humanized mice, we show that broadly neutralizing antibodies (bNAbs) can interfere with establishment of a silent reservoir by Fc-FcR-mediated mechanisms. In established infection, bNAbs or bNAbs plus single inducers are ineffective in preventing viral rebound. However, bNAbs plus a combination of inducers that act by independent mechanisms synergize to decrease the reservoir as measured by viral rebound. Thus, combinations of inducers and bNAbs constitute a therapeutic strategy that impacts the establishment and maintenance of the HIV-1 reservoir in humanized mice.
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•bNAbs can be used for postexposure prophylaxis (PEP) in humanized mice•bNAb PEP efficacy requires Fc-receptor binding•bNAbs plus a single inducer of HIV-1 transcription do not reduce viral rebound•bNAbs plus a combination of inducers significantly reduce viral rebound
A combination of broadly neutralizing antibodies and viral inducers reduce the frequency of viral rebound in the humanized mouse model of HIV-1 infection.
Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it ...has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.
Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization ...breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env’s silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3Å cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448gp120 glycan. Effective bNAbs can therefore be raised against HIV-1 Env’s silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development.
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•Silentface (SF) bNAbs can reach substantial neutralization breadth and potency•Defined structure of a SF bNAb bound to an Env trimer•Binding of SF bNAb resulted in trimer asymmetry in the V3 region•SF antibodies have in vivo activity and potential for clinical use
VRC-PG05 was the only donor-derived antibody against the silentface (SF) of HIV-1 envelope described to date. Schoofs et al. identify the antibody SF12 and its relatives, which recognize the center of the SF with a different angle and more extensive protein recognition than VRC-PG05, thereby achieving substantial neutralizing ability and potential for clinical use.
The arrival of COVID-19 in Brazil and the accelerated process of dissemination/contamination added to the evolution of the clinical picture of the disease, and the saturation of the capacity of ...health services, creating new challenges for researchers, governments, and professionals involved in the occupational health area.
This article aims to systematize and synthesize the proposals adopted by the legislation and by the Brazilian State, with a focus on worker protection and guaranteeing a safe work environment for the performance of their professional activities.
This is qualitative bibliographical research of the narrative literature review type, developed from October 2020 to June 2021 in legislation databases using the strategy: "COVID-19" AND "coronavirus/coronavirus" AND "worker health" on official Brazilian government websites.
The lack of an emergency plan for efficient actions to respond to the epidemic caused and is still causing the daily deaths of workers.
There is a need to guarantee the effectiveness of national and international policies and norms that have been neglected by the Brazilian government.
The CD4 binding site (CD4bs) on the envelope glycoprotein is a major site of vulnerability that is conserved among different HIV-1 isolates. Many broadly neutralizing antibodies (bNAbs) to the CD4bs ...belong to the VRC01 class, sharing highly restricted origins, recognition mechanisms and viral escape pathways. We sought to isolate new anti-CD4bs bNAbs with different origins and mechanisms of action. Using a gp120 2CC core as bait, we isolated antibodies encoded by IGVH3-21 and IGVL3-1 genes with long CDRH3s that depend on the presence of the N-linked glycan at position-276 for activity. This binding mode is similar to the previously identified antibody HJ16, however the new antibodies identified herein are more potent and broad. The most potent variant, 179NC75, had a geometric mean IC80 value of 0.42 μg/ml against 120 Tier-2 HIV-1 pseudoviruses in the TZM.bl assay. Although this group of CD4bs glycan-dependent antibodies can be broadly and potently neutralizing in vitro, their in vivo activity has not been tested to date. Here, we report that 179NC75 is highly active when administered to HIV-1-infected humanized mice, where it selects for escape variants that lack a glycan site at position-276. The same glycan was absent from the virus isolated from the 179NC75 donor, implying that the antibody also exerts selection pressure in humans.
Abstract Introduction: Inclusion programs for students with disabilities in Federal Institutions of Higher Education (IFES) seek to favor access and permanence based on respect for diversity in the ...university environment. The Occupational Therapy can help developing these programs. Objective: To analyze the access of the population with disabilities to higher education, considering the premises of the Inclusion Program INCLUIR of the Ministry of Education. Reflect on the contribution of occupational therapists in this program. Method: The descriptive-analytical research based on documentary analysis identified 55 Inclusion Program centers in the IFES, recognizing the developed actions. We studied the curriculum and research groups in the IFES with an occupational therapy course regarding this subject. We interviewed three occupational therapists that coordinated these programs. Results: We observed progress in the inclusion of people with disabilities in higher education, encouraged by government programs. The occupational therapy curriculum of the 14 IFES, as well as their research groups, do not indicate activities in the area of Education, which would make it difficult to practice professional technical actions in the area. Eight of the 55 nuclei have occupational therapists with a differential action of the professional capacity to perceive and favor the contact with the diversity of realities among students, which would potentialize equalization actions in the daily academic life, especially the permanence of people with deficiency. Conclusion: There is an urgent need to increase inclusion programs and the participation of occupational therapist, to increase the organization and management of actions for more dialogue between the IFES instances and to favor the entry and stay of students with disabilities.
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