Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood ...immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.
The UiO-66 metal–organic framework has remarkable physicochemical characteristics which have positioned it as one of the Zr-MOFs with greater potential for application in diverse processes. However, ...it remains a challenge how to optimize the synthesis methods so as to obtain this material with high yield and good porous properties under more eco-compatible conditions. In this work, we report the solvothermal synthesis of UiO-66 nanocrystals with high surface area using acetone as the synthesis medium, replacing the traditional and toxic
N
,
N
-dimethylformamide. The effects of solvents, reactant concentration, temperature, synthesis time and mixture protocol on the material properties were characterized by XRD, SEM–EDS, FTIR, TGA-SDTA and
N
2
adsorption isotherms. The sample obtained in pure acetone employing the optimized protocol exhibited spherical nanoparticles 150 nm in size and presented the greatest relative crystallinity. The alternative protocol allowed obtaining UiO-66 with high yields (~ 91%) without employing DMF, under mild conditions (80 °C), in the form of nanocrystals with high specific surface area (1299 m
2
g
−1
) that can be activated by simple drying at 130 °C and atmospheric pressure. The MOF obtained in acetone under optimum conditions showed reversible CO
2
uptake capacity at room temperature and low pressures as determined by both CO
2
isotherms and TGA-CO
2
tests.
Members of the family Trypanosomatidae infect many organisms, including animals, plants and humans. Plant-infecting trypanosomes are grouped under the single genus Phytomonas, failing to reflect the ...wide biological and pathological diversity of these protists. While some Phytomonas spp. multiply in the latex of plants, or in fruit or seeds without apparent pathogenicity, others colonize the phloem sap and afflict plants of substantial economic value, including the coffee tree, coconut and oil palms. Plant trypanosomes have not been studied extensively at the genome level, a major gap in understanding and controlling pathogenesis. We describe the genome sequences of two plant trypanosomatids, one pathogenic isolate from a Guianan coconut and one non-symptomatic isolate from Euphorbia collected in France. Although these parasites have extremely distinct pathogenic impacts, very few genes are unique to either, with the vast majority of genes shared by both isolates. Significantly, both Phytomonas spp. genomes consist essentially of single copy genes for the bulk of their metabolic enzymes, whereas other trypanosomatids e.g. Leishmania and Trypanosoma possess multiple paralogous genes or families. Indeed, comparison with other trypanosomatid genomes revealed a highly streamlined genome, encoding for a minimized metabolic system while conserving the major pathways, and with retention of a full complement of endomembrane organelles, but with no evidence for functional complexity. Identification of the metabolic genes of Phytomonas provides opportunities for establishing in vitro culturing of these fastidious parasites and new tools for the control of agricultural plant disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR). Design Multicenter, randomized, ...placebo-controlled, double-blinded prospective design. Setting Fourteen Scandinavian fertility clinics. Patient(s) A total of 1,332 women with indication for in vitro fertilization or intracytoplasmic sperm injection; 1,149 received embryo transfer (GM-CSF: n = 564; control: n = 585). Intervention(s) Oocytes were fertilized, and embryos cultured and transferred in control medium or test medium containing 2 ng/mL GM-CSF. Main Outcome Measure(s) OIR at gestational week 7, with follow-up at week 12 and birth. Result(s) At week 7, OIRs were 23.5% (GM-CSF), and 20.0% (control) (odds ratio OR 1.26, 95% confidence interval CI 0.91–1.75). At week 12, OIRs were 23.0% (GM-CSF) and 18.7% (control) (OR 1.35, 95% CI 1.06–1.72), and live birth rates were 28.9% and 24.1%, respectively (OR 1.35, 95% CI 1.03–1.78). The effect of GM-CSF was influenced by the human serum albumin concentration in the medium. Birth weight and abnormality incidence were similar in both groups. Exploratory analyses showed that GM-CSF increased OIR in women with previous miscarriage, especially in women with more than one miscarriage. Conclusion(s) Addition of GM-CSF to embryo culture medium elicits a significant increase in survival of transferred embryos to week 12 and live birth. Our results are consistent with a protective effect of GM-CSF on culture-induced embryo stress. GM-CSF may be particularly efficacious in women with previous miscarriage. Clinical Trial Registration Number NCT00565747.
Coronavirus disease 2019 (COVID-19) is currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional cytometry to analyze 125 COVID-19 ...patients and compare them with recovered and healthy individuals. Integrated analysis of ~200 immune and ~50 clinical features revealed activation of T cell and B cell subsets in a proportion of patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses reaching >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable with that in uninfected individuals. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. Our analyses identified three immunotypes associated with poor clinical trajectories versus improving health. These immunotypes may have implications for the design of therapeutics and vaccines for COVID-19.
Viral gastroenteritis causes high morbidity worldwide. In this study, stool samples from 179 children aged 0-6 years attending Danish day care centers were investigated for gastrointestinal viruses. ...Each child was observed for one year with submission of samples and questionnaires every two months. Adenovirus, norovirus, rotavirus, and sapovirus were detected in samples using real-time PCR. A total of 229 (33%) of the 688 samples collected tested positive for at least one virus. At the first sampling point, adenovirus was shed by 6%, norovirus genotype I by 3% and genotype II by 12%, rotavirus A by 9%, and sapovirus by 21% of the 142 children included in the risk factor analyses. Increasing age was identified as a protective factor against testing positive for gastrointestinal virus, whereas nausea during the previous two months was positively associated with testing positive. Odds of shedding adenovirus were 9.6 times higher among children treated with antibiotics within the previous two months than among children who were not. Gastrointestinal viruses were shed year-round and high viral loads were observed in samples from both symptomatic and asymptomatic children, suggesting children in day care as a reservoir and a possible source of spreading of viruses into the community.
The clinical outcome of colorectal cancer (CRC) is associated with the immune response; thus, these tumors could be responsive to different immune therapy approaches. Natural killer (NK) cells are ...key antitumor primary effectors that can eliminate CRC cells without prior immunization. We previously determined that NK cells from the local tumor environment of CRC tumors display a profoundly altered phenotype compared with circulating NK cells from healthy donors (HD). In this study, we evaluated peripheral blood NK cells from untreated patients and their possible role in metastasis progression. We observed profound deregulation in receptor expression even in early stages of disease compared with HD. CRC-NK cells displayed underexpression of CD16, NKG2D, DNAM-1, CD161, NKp46, and NKp30 activating receptors, while inhibitory receptors CD85j and NKG2A were overexpressed. This inhibited phenotype affected cytotoxic functionality against CRC cells and interferon-γ production. We also determined that NKp30 and NKp46 are the key receptors involved in detriment of CRC-NK cells' antitumor activity. Moreover, NKp46 expression correlated with relapse-free survival of CRC patients with a maximum follow-up of 71 months. CRC-NK cells also exhibited altered antibody-dependent cellular cytotoxicity function responding poorly to cetuximab. IL-2 and IL-15 in combination with cetuximab stimulated NK cell, improving cytotoxicity. These results show potential strategies to enhance CRC-NK cell activity.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to ...other antigenically distinct common seasonal human coronaviruses (hCoVs) before the coronavirus disease 2019 (COVID-19) pandemic. Here, we quantified levels of SARS-CoV-2-reactive antibodies and hCoV-reactive antibodies in serum samples collected from 431 humans before the COVID-19 pandemic. We then quantified pre-pandemic antibody levels in serum from a separate cohort of 251 individuals who became PCR-confirmed infected with SARS-CoV-2. Finally, we longitudinally measured hCoV and SARS-CoV-2 antibodies in the serum of hospitalized COVID-19 patients. Our studies indicate that most individuals possessed hCoV-reactive antibodies before the COVID-19 pandemic. We determined that ∼20% of these individuals possessed non-neutralizing antibodies that cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins. These antibodies were not associated with protection against SARS-CoV-2 infections or hospitalizations, but they were boosted upon SARS-CoV-2 infection.
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•Some humans possessed cross-reactive SARS-CoV-2 antibodies prior to the pandemic•Pre-pandemic SARS-CoV-2 reactive antibodies are not associated with protection•Antibodies to a related betacoronavirus are boosted upon SARS-CoV-2 infection
Analysis of human serum samples before and after the onset of the COVID-19 pandemic show that antibodies against common seasonal human coronaviruses are cross-reactive against SARS-CoV-2 but do not confer cross-protection against infection or hospitalization.
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•Chemometrics methods used to verify the similarity between petroleum samples.•PCA was used to reduce the dimensionality of the data.•From FTIR spectra it is possible to determine the ...profile of petroleum.•FTIR spectra reach the same conclusion as physical-chemical property assay.
The petroleum industry has the interest to know the physicochemical properties of the crude oil before its exploration in order to estimate its costs with processing, transportation, storage and refining. The profile of the recovered oil is determined by the analysis of some physicochemical properties, which may require a long time or a large volume of the sample, delaying decision-making on production and refining. Spectroscopic techniques allow the acquisition of a large amount of information about the sample at a molecular level, in a short time, and with a small amount of sample. This paper aims to identify petroleum profiles using a spectroscopy technique in the middle infrared region associated with methods of standards recognition PCA and kNN. We used 81 oils, divided into two groups: 69 samples of the training set (model construction) and 12 samples of the test set (model performance verification). For all samples, MIR spectra were acquired and measurements of 13 physicochemical properties were obtained. The results show that the methodology using MIR spectroscopy with chemometrics makes it possible to obtain equivalent conclusions about the most similar crude oils, that is, with similar behaviors, when we analyze a database with 13 physicochemical properties of the crude oils.
•Subjects rated pleasantness, wanting, and disgust towards positive and negative foods.•An indirect approach-avoidance task assessed their motivational tendencies.•Ratings reflected extreme ...reactions, revealing a strong effect of the food category.•Implicit measures were more sensitive to study rejection to negative foods.
Wanting and rejecting food are natural reactions that we humans all experience, often unconsciously, on a daily basis. However, in the food domain, the focus to date has primarily been on the approach tendency, and researchers have tended not to study the two opposing tendencies in a balanced manner. Here, we develop a methodology with which to understand people's implicit and explicit reactions to both positive (appealing) and negative (disgusting) foods. It consists of a combination of direct and indirect computer-based tasks, as well as a validated food image stimulus set, specifically designed to investigate motivational approach and avoidance responses towards foods. Fifty non-dieting participants varying in terms of their hunger state (hungry vs. not hungry) reported their explicit evaluations of pleasantness, wanting, and disgust towards the idea of tasting each of the food images that were shown. Their motivational tendencies towards those food items were assessed indirectly using a joystick-based approach-avoidance procedure. For each of the food images that were presented, the participants had to move the joystick either towards or away from themselves (approach and avoidance movements, respectively) according to some unrelated instructions, while their reaction times were recorded. Our findings demonstrated the hypothesised approach–avoidance compatibility effect: a significant interaction of food valence and direction of movement. Furthermore, differences between the experimental groups were observed. The participants in the no-hunger group performed avoidance (vs. approach) movements significantly faster; and their approach movements towards positive (vs. negative) foods were significantly faster. As expected, the self-report measures revealed a strong effect of the food category on the three dependent variables and a strong main effect of the hunger state on wanting and to a lesser extent on pleasantness.
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