Machine learning models are revolutionizing our approaches to discovering and designing bioactive peptides. These models often need protein structure awareness, as they heavily rely on sequential ...data. The models excel at identifying sequences of a particular biological nature or activity, but they frequently fail to comprehend their intricate mechanism(s) of action. To solve two problems at once, we studied the mechanisms of action and structural landscape of antimicrobial peptides as (i) membrane-disrupting peptides, (ii) membrane-penetrating peptides, and (iii) protein-binding peptides. By analyzing critical features such as dipeptides and physicochemical descriptors, we developed models with high accuracy (86-88%) in predicting these categories. However, our initial models (1.0 and 2.0) exhibited a bias towards α-helical and coiled structures, influencing predictions. To address this structural bias, we implemented subset selection and data reduction strategies. The former gave three structure-specific models for peptides likely to fold into α-helices (models 1.1 and 2.1), coils (1.3 and 2.3), or mixed structures (1.4 and 2.4). The latter depleted over-represented structures, leading to structure-agnostic predictors 1.5 and 2.5. Additionally, our research highlights the sensitivity of important features to different structure classes across models.
Background
Rheumatoid arthritis (RA) patients are at increased risk of insulin resistance (IR); however, the specific mechanisms mediating this association are currently unknown.
Objective
To ...investigate whether the inflammatory activity associated with RA accounts for the observed defective glucose metabolism and lipid metabolism in these patients.
Methods
We followed two main strategies: (i) extensive metabolic profiling of a RA cohort of 100 patients and 50 healthy control subjects and (ii) mechanistic studies carried out in both a collagen‐induced arthritis mouse model and 3T3‐L1 adipocytes treated with conditioned serum from RA patients.
Results
Following the exclusion of obese and diabetic subjects, data from RA patients demonstrated a strong link between the degree of systemic inflammation and the development of IR. These results were strengthened by the observation that induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in different tissues. Adipose tissue was most susceptible to the RA‐induced metabolic alterations. These metabolic effects were confirmed in adipocytes treated with serum from RA patients.
Conclusions
Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA.
Purpose of Review
Evidence suggests that the microbiome of the skin, gastrointestinal tract, and airway contribute to health and disease. As we learn more about the role that the microbiota plays in ...allergic disease development, we can develop therapeutics to alter this pathway.
Recent Findings
Epidemiologic studies reveal that an association exists between environmental exposures, which alter the microbiota, and developing atopic dermatitis, food allergy, and/or asthma. In fact, samples from the skin, gastrointestinal tract, and respiratory tract reveal distinct microbiotas compared with healthy controls, with microbial changes (dysbiosis) often preceding the development of allergic disease. Mechanistic studies have confirmed that microbes can either promote skin, gut, and airway health by strengthening barrier integrity, or they can alter skin integrity and damage gut and airway epithelium.
Summary
In this review, we will discuss recent studies that reveal the link between the microbiota and immune development, and we will discuss ways to influence these changes.
Context.
Lithium is one of the few elements produced during Big Bang nucleosynthesis in the early universe. Moreover, its fragility makes it useful as a proxy for stellar environmental conditions. As ...such, the lithium abundance in old systems is at the core of various astrophysical investigations.
Aims.
Stars on the lower red giant branch are key to studies of globular clusters where main sequence stars are too faint to be observed. We use these stars to analyze the initial Li content of the clusters and compare it to cosmological predictions, to measure spreads in Li between different stellar populations, and to study signs of extra depletion in these giants.
Methods.
We used the GIRAFFE spectra to measure the lithium and sodium abundances of lower red giant branch stars in five globular clusters. These cover an extensive range in metallicity, from Fe/H ∼ −0.7 to Fe/H ∼ −2.3 dex.
Results.
We find that the lithium abundance in these lower red giant branch stars forms a plateau, with values from
A
(Li)
NLTE
= 0.84 to 1.03 dex, showing no clear correlation with metallicity. When using stellar evolutionary models to calculate the primordial abundance of these clusters, we recover values of
A
(Li)
NLTE
= 2.1 − 2.3 dex, consistent with the constant value observed in warm metal-poor halo stars, namely the Spite plateau. Additionally, we find no difference in the lithium abundance of first and second population stars in each cluster. We also report the discovery of a Li-rich giant in the cluster NGC 3201, with
A
(Li)
NLTE
= 1.63 ± 0.18 dex, where the enrichment mechanism is probably pollution from external sources.
Abstract Objectives 1) To assess the association of NETosis and NETosis-derived products with the activity of the disease and the development of cardiovascular disease in RA; 2) To evaluate the ...involvement of NETosis on the effects of biologic therapies such as anti-TNF alpha (Infliximab) and anti-IL6R drugs (Tocilizumab). Methods One hundred and six RA patients and 40 healthy donors were evaluated for the occurrence of NETosis. Carotid-intimae media thickness was analyzed as early atherosclerosis marker. Inflammatory and oxidative stress mediators were quantified in plasma and neutrophils. Two additional cohorts of 75 RA patients, treated either with Infliximab (n = 55) or Tocilizumab (n = 20) for six months, were evaluated. Results NETosis was found increased in RA patients, beside myeloperoxidase and neutrophil elastase protein levels. Cell-free nucleosomes plasma levels were elevated, and strongly correlated with the activity of the disease and the positivity for autoantibodies, alongside inflammatory and oxidative profiles in plasma and neutrophils. Moreover, ROC analyses showed that cell-free nucleosomes levels could identify RA patients showing early atherosclerosis with high specificity. RA patients treated either with IFX or TCZ for six months exhibited decreased generation of NETs. Concomitantly, clinical parameters and serum markers of inflammation were found reduced. Mechanistic in vitro analyses showed that inhibition of NETs extrusion by either DNase, IFX or TCZ, further abridged the endothelial dysfunction and the activation of immune cells, thus influencing the global activity of the vascular system. Conclusions NETosis-derived products may have diagnostic potential for disease activity and atherosclerosis, as well as for the assessment of therapeutic effectiveness in RA.
Context. Large spectroscopic surveys devoted to the study of the Milky Way, including Gaia, use automated pipelines to determine the atmospheric parameters of millions of stars. The Gaia FGK ...benchmark stars are reference stars with Teff and log ?? derived through fundamental relations, independently of spectroscopy, to be used as anchors for the parameter scale. The first and second versions of the sample have been extensively used for that purpose, and more generally to help constrain stellar models. Aims. We provide the third version of the Gaia FGK benchmark stars, an extended set intended to improve the calibration of spectroscopic surveys, and their interconnection. Methods. We have compiled about 200 candidates that have precise measurements of angular diameters and parallaxes. We determined their bolometric fluxes by fitting their spectral energy distribution. Masses were determined using two sets of stellar evolution models. In a companion paper, we describe the determination of metallicities and detailed abundances. Results. We provide a new set of 192 Gaia FGK benchmark stars with their fundamental Teff and log ??, and with uncertainties lower than 2% for most stars. Compared to the previous versions, the homogeneity and accuracy of the fundamental parameters are significantly improved thanks to the high quality of the Gaia photometric and astrometric data.
We evaluated the MYD88 L265P mutation in Waldenström's macroglobulinemia (WM) and B-cell lymphoproliferative disorders by specific polymerase chain reaction (PCR) (sensitivity ∼10(-3)). No mutation ...was seen in normal donors, while it was present in 101/117 (86%) WM patients, 27/31 (87%) IgM monoclonal gammapathies of uncertain significance (MGUS), 3/14 (21%) splenic marginal zone lymphomas and 9/48 (19%) non-germinal center (GC) diffuse large B-cell lymphomas (DLBCLs). The mutation was absent in all 28 GC-DLBCLs, 13 DLBCLs not subclassified, 35 hairy cell leukemias, 39 chronic lymphocytic leukemias (16 with M-component), 25 IgA or IgG-MGUS, 24 multiple myeloma (3 with an IgM isotype), 6 amyloidosis, 9 lymphoplasmacytic lymphomas and 1 IgM-related neuropathy. Among WM and IgM-MGUS, MYD88 L265P mutation was associated with some differences in clinical and biological characteristics, although usually minor; wild-type MYD88 cases had smaller M-component (1.77 vs 2.72 g/dl, P=0.022), more lymphocytosis (24 vs 5%, P=0.006), higher lactate dehydrogenase level (371 vs 265 UI/L, P=0.002), atypical immunophenotype (CD23-CD27+ +FMC7+ +), less Immunoglobulin Heavy Chain Variable gene (IGHV) somatic hypermutation (57 vs 97%, P=0.012) and less IGHV3-23 gene selection (9 vs 27%, P=0.014). These small differences did not lead to different time to first therapy, response to treatment or progression-free or overall survival.
We report the discovery of planetary companions orbiting four low-luminosity giant stars with
M
⋆
between 1.04 and 1.39
M
⊙
. All four host stars have been independently observed by the EXoPlanets ...aRound Evolved StarS (EXPRESS) program and the Pan-Pacific Planet Search (PPPS). The companion signals were revealed by multi-epoch precision radial velocities obtained in nearly a decade. The planetary companions exhibit orbital periods between ~1.2 and 7.1 yr, minimum masses of
m
p
sin
i
~ 1.8–3.7
M
J
, and eccentricities between 0.08 and 0.42. With these four new systems, we have detected planetary companions to 11 out of the 37 giant stars that are common targets in the EXPRESS and PPPS. After excluding four compact binaries from the common sample, we obtained a fraction of giant planets (
m
p
≳ 1– 2
M
J
) orbiting within 5 AU from their parent star of
f
= 33.3
−7.1
+9.0
%. This fraction is slightly higher than but consistent at the 1
σ
level with previous results obtained by different radial velocity surveys. Finally, this value is substantially higher than the fraction predicted by planet formation models of gas giants around stars more massive than the Sun.
Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after ...therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾10
cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.
Migrant women at risk of social exclusion often experience health inequities based on gender, country of origin or socioeconomic status. Traditional health promotion programs designed for this ...population have focused on covering their basic needs or modifying lifestyle behaviors. The salutogenic model of health could offer a new perspective enabling health promotion programs to reduce the impact of health inequities. This study evaluated the effectiveness of a salutogenic health promotion program focused on the empowerment of migrant women at risk of social exclusion.
A four-session salutogenic health promotion program was conducted over a period of 6 months. In a quasi-experimental pre-test post-test design, an ad hoc questionnaire was administered to 26 women to collect sociodemographic data, together with 5 validated instruments: Antonovsky's Sense of Coherence (SOC-13), Duke-UNC-11 (perceived social support), Quality of Life Short Form-36 (SF-36), Rosenberg's Self-Esteem Scale, and the Cohen et al. Perceived Stress Scale (PSS-10). Descriptive analysis and multiple linear regression models were performed. Statistical tests were considered significant with a two-tailed p value < 0.05.
Participants had a low initial SOC-13 score (60.36; SD 8.16), which did not show significant change after the health promotion program. Perceived social support (37.07; SD 6.28) and mental quality of life also remained unchanged, while physical quality of life increased from 50.84 (SD 4.60) to 53.08 (SD 5.31) (p = 0.049). Self-esteem showed an increasing trend from 30.14 (SD 4.21) to 31.92 (SD 4.38) (p = 0.120). Perceived stress decreased from 20.57 (SD 2.91) to 18.38 (SD 3.78) (p = 0.016). A greater effect was observed at the end of the program in women with lower initial scores for SOC-13 and quality of life and higher initial scores of perceived stress.
The health promotion program reduced perceived stress, increased physical quality of life and showed a trend toward increased self-esteem, especially among migrant women with multiple vulnerability factors. The salutogenic model of health should be considered as a good practice to apply in health promotion programs and to be included in national policies to reduce health inequity in migrant populations.
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