Recent advances in high-throughput single cell sequencing have opened up new avenues into the investigation of B cell receptor (BCR) repertoires. In this study, PBMCs were collected from 17 human ...participants vaccinated with the split-inactivated influenza virus vaccine during the 2016-2017 influenza season. A combination of Immune Repertoire Capture (IRCTM) technology and IgG sequencing was performed on ~7,800 plasmablast (PB) cells and preferential IgG heavy-light chain pairings were investigated. In some participants, a single expanded clonotype accounted for ~22% of their PB BCR repertoire. Approximately 60% (10/17) of participants experienced convergent evolution, possessing public PBs that were elicited independently in multiple participants. Binding profiles of one private and three public PBs confirmed they were all subtype-specific, cross-reactive hemagglutinin (HA) head-directed antibodies. Collectively, this high-resolution antibody repertoire analysis demonstrated the impact evolution can have on BCRs in response to influenza virus vaccination, which can guide future universal influenza prophylactic approaches.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Salmonellosis and listeriosis together accounted for more than one third of foodborne illnesses in the United States and almost half the hospitalizations for gastrointestinal diseases in 2018 while ...tuberculosis afflicted over 10 million people worldwide causing almost 2 million deaths. Regardless of the intrinsic virulence differences among Listeria monocytogenes, Salmonella enterica and Mycobacterium tuberculosis, these intracellular pathogens share the ability to survive and persist inside the macrophage and other cells and thrive in iron rich environments. Interferon-gamma (IFN-γ) is a central cytokine in host defense against intracellular pathogens and has been shown to promote iron export in macrophages. We hypothesize that IFN-γ decreases iron availability to intracellular pathogens consequently limiting replication in these cells. In this study, we show that IFN-γ regulates the expression of iron-related proteins hepcidin, ferroportin, and ferritin to induce iron export from macrophages. Listeria monocytogenes, S. enterica, and M. tuberculosis infections significantly induce iron sequestration in human macrophages. In contrast, IFN-γ significantly reduces hepcidin secretion in S. enterica and M. tuberculosis infected macrophages. Similarly, IFN-γ-activated macrophages express higher ferroportin levels than untreated controls even after infection with L. monocytogenes bacilli; bacterial infection greatly down-regulates ferroportin expression. Collectively, IFN-γ significantly inhibits pathogen-associated intracellular iron sequestration in macrophages and consequently retards the growth of intracellular bacterial pathogens by decreasing iron availability.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tuberculosis (TB) has been a transmittable human disease for many thousands of years, and
is again the number one cause of death worldwide due to a single infectious agent. The intense 6- to 10-month ...process of multi-drug treatment, combined with the adverse side effects that can run the spectrum from gastrointestinal disturbances to liver toxicity or peripheral neuropathy are major obstacles to patient compliance and therapy completion. The consequent increase in multidrug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) cases requires that we increase our arsenal of effective drugs, particularly novel therapeutic approaches. Over the millennia, host and pathogen have evolved mechanisms and relationships that greatly influence the outcome of infection. Understanding these evolutionary interactions and their impact on bacterial clearance or host pathology will lead the way toward rational development of new therapeutics that favor enhancing a host protective response. These host-directed therapies have recently demonstrated promising results against
, adding to the effectiveness of currently available anti-mycobacterial drugs that directly kill the organism or slow mycobacterial replication. Here we review the host-pathogen interactions during
infection, describe how
bacilli modulate and evade the host immune system, and discuss the currently available host-directed therapies that target these bacterial factors. Rather than provide an exhaustive description of
virulence factors, which falls outside the scope of this review, we will instead focus on the host-pathogen interactions that lead to increased bacterial growth or host immune evasion, and that can be modulated by existing host-directed therapies.
Influenza is a highly contagious viral respiratory disease that affects millions of people worldwide each year. Annual vaccination is recommended by the World Health Organization to reduce influenza ...severity and limit transmission through elicitation of antibodies targeting mainly the hemagglutinin glycoprotein of the influenza virus. Antibodies elicited by current seasonal influenza vaccines are predominantly strain-specific. However, continuous antigenic drift by circulating influenza viruses facilitates escape from pre-existing antibodies requiring frequent reformulation of the seasonal influenza vaccine. Traditionally, immunological responses to influenza vaccination have been largely focused on IgG antibodies, with almost complete disregard of other isotypes. In this report, young adults (18-34 years old) and elderly (65-85 years old) subjects were administered the split inactivated influenza vaccine for 3 consecutive seasons and their serological IgA and IgG responses were profiled. Moreover, correlation analysis showed a positive relationship between vaccine-induced IgA antibody titers and traditional immunological endpoints, exposing vaccine-induced IgA antibodies as an important novel immune correlate during influenza vaccination.
Iron is a crucial micronutrient for both mammals and their associated pathogens, and extensive literature has shown that Mycobacterium tuberculosis (Mtb) bacilli inhibited from acquiring iron from ...the host are severely attenuated. In contrast, increased dietary iron concentrations or patients with hemochromatosis have long been associated with a more severe tuberculosis (TB) disease outcome. We have observed that upon macrophage infection, Mtb bacilli strongly promote intracellular iron sequestration, both through increased expression of hepcidin, a key mammalian iron regulatory protein, and downregulation of the iron exporter protein, ferroportin. Heparin is a highly sulfated glycosaminoglycan released by mast cells and basophils at sites of tissue injury. During Mtb infection, heparin alters intracellular trafficking in alveolar epithelial cells and decreases extrapulmonary dissemination but recently, heparin also has been reported to inhibit hepcidin expression in hepatocytes, decreasing intracellular iron availability. In this report, we demonstrate that heparin significantly reduces hepcidin expression in macrophages infected with Mtb bacilli. Heparin-treated macrophages have higher ferroportin expression compared to untreated macrophages, promoting iron export and decreasing iron availability to intracellular bacilli. Thus, here we describe a novel immunomodulatory effect and potential therapeutic role for heparin against mycobacterial infection in human macrophages.
Influenza is a highly contagious viral respiratory disease that affects million of people worldwide each year. Annual vaccination is recommended by the World Health Organization with the goal of ...reducing influenza severity and limiting transmission through elicitation of antibodies targeting the hemagglutinin (HA) glycoprotein. The antibody response elicited by current seasonal influenza virus vaccines is predominantly strain-specific, but pre-existing influenza virus immunity can greatly impact the serological antibody response to vaccination. However, it remains unclear how B cell memory is shaped by recurrent annual vaccination over the course of multiple seasons, especially in high-risk elderly populations. Here, we systematically profiled the B cell response in young adult (18-34 year old) and elderly (65+ year old) vaccine recipients that received annual split inactivated influenza virus vaccination for 3 consecutive seasons. Specifically, the antibody serological and memory B-cell compartments were profiled for reactivity against current and historical influenza A virus strains. Moreover, multiparametric analysis and antibody landscape profiling revealed a transient increase in strain-specific antibodies in the elderly, but with an impaired recall response of pre-existing memory B-cells, plasmablast (PB) differentiation and long-lasting serological changes. This study thoroughly profiles and compares the immune response to recurrent influenza virus vaccination in young and elderly participants unveiling the pitfalls of current influenza virus vaccines in high-risk populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate macular vasculature in diabetic retinopathy (DR) with optical coherence tomography angiography (OCTA) and to correlate vessel density (VD) with retinal sensitivity (RS) as a way to assess ...structural and functional findings in DR.
Prospective observational cross-sectional study.
Diabetic patients with DR but no clinically significant diabetic macular edema (DME) and healthy subjects were included in this study. All of them underwent comprehensive ophthalmic examination, best corrected visual acuity (BCVA), OCTA with RS-3000 Advance AngioScan (Nidek, Gamagori, Japan) and microperimetry with MP-3 (Nidek, Gamagori, Japan). Retinal vascular density measured by OCT angiography in 9 areas was correlated with RS in the same 9 areas by Spearman correlation.
In this study, 50 subjects were enrolled: 25 eyes of diabetic patients with DR and 25 eyes of non-diabetic subjects. Diabetic patients mean age was 51.88±13.62 years; non-diabetic subjects were 43.48±13.42 years. The BCVA was 20/25 in the diabetic group and 20/20 in the non-diabetic group. Mean RS was decreased in the DR group (27.68±2.71 dB) compared to the non-diabetic group (31.68±1.46 dB) (p<0.05) and in the 9 studied areas (p<0.05). Mean VD was decreased in the DR group compared to non-diabetics (p<0.05) and in 7 of the 9 areas (except temporal superior and inferior squares) (p<0.05). Correlations by areas between VD and RS were assessed, we found moderate correlation in the area temporal to the fovea (r=0.501, p=0.01) in the DR group but not in the non-diabetic subjects. There were no other statistical significant correlations with this pattern.
DR without DME results in a retinal VD decreased that might be the cause of a reduction of RS in one of the studied areas. Microangiopathic changes are correlated with microperimetry sensitivity drop in the temporal to the fovea grid but not in the other studied grids.
As the COVID-19 pandemic continues, the authorization of vaccines for emergency use has been crucial in slowing down the rate of infection and transmission of the SARS-CoV-2 virus that causes ...COVID-19. In order to investigate the longitudinal serological responses to SARS-CoV-2 natural infection and vaccination, a large-scale, multi-year serosurveillance program entitled SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) was initiated at 4 locations in the U.S. The serological assay presented here measuring IgG binding to the SARS-CoV-2 receptor binding domain (RBD) detected antibodies elicited by SARS-CoV-2 infection or vaccination with a 95.5% sensitivity and a 95.9% specificity. We used this assay to screen more than 3100 participants and selected 20 previously infected pre-immune and 32 immunologically naïve participants to analyze their antibody binding to RBD and viral neutralization (VN) responses following vaccination with two doses of either the Pfizer-BioNTech BNT162b2 or the Moderna mRNA-1273 vaccine. Vaccination not only elicited a more robust immune reaction than natural infection, but the level of neutralizing and anti-RBD antibody binding after vaccination is also significantly higher in pre-immune participants compared to immunologically naïve participants (
p
<0.0033). Furthermore, the administration of the second vaccination did not further increase the neutralizing or binding antibody levels in pre-immune participants (
p
=0.69). However, ~46% of the immunologically naïve participants required both vaccinations to seroconvert.
Oil spills cause severe environmental and economic impacts, so the use of bioremediation techniques has been widely studied to solve this problem. Due to its complex composition, the oil prevents the ...full action of microorganisms, and in this way, the microbial consortium encapsulation technique is an innovation in the use of bacteria and biomass in the face of possible oil degradation, with the possibility of overcoming techniques such as bio-enhancement and biostimulation in the face of factors such as nutrient availability, oxygenation and temperature. Therefore, this work aims to produce capsules containing microbiological consortium and analyze its characteristics using the techniques TGA, DSC, FESEM, viable cell count, emulsification index and surface tension, in order to propose the best conditions to be applied. TGA and DSC results showed that the capsules have thermal stability in the range of 25–40 °C. Viable cell counts were more effective in capsules containing 1% (w/v) sodium alginate, and the emulsification index showed a large increase (80%) from day 5, as well as surface tension had a large drop (48%) in the same period. The increase in the emulsification index is caused by the increase in the production of biosurfactants (amphipathic molecules) by the bacteria consortium and this offers a greater contact between the microorganisms and the oil, providing best conditions for the degradation of oil. Therefore, all analyzes showed excellent results for future application in oil spills.
Human creativity finds in artistic practices one of its most admirable forms. Most of the studies about artistic practices have used qualitative approaches, focusing on the conceptual structures ...conveyed by the artwork. Few studies have used quantitative approaches with the potential to be generalized. This study has focused on developing a quantitative methodology to characterize an artist’s behavioral patterns while creating an artwork. Inspired by a theoretical framework from animal cognition, we analyzed the decision‐making process of an artist while choosing to invest more or less effort in given elements of the art piece. We have video recorded the rehearsals of a dance piece and hand‐scored the movement phrases elicited individually by two dancers and quantitatively reconstructed the sequence of movement phrases being performed at each moment. This representation has revealed, implicitly, that the choreographer invested more energy in creating movement sequences, and that certain elements of movement were more prone to several iterations. Our study shows that decision‐making processes in artistic practices can be revealed through the use of quantitative methodologies which can be potentially generalized to other choreographic methodologies and styles, thus leading to a better understanding of those artistic practices and, generally, of human creative behavior.
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