Molecular relapse monitoring reveals the domination of impaired NK cell education over impaired inhibition in missing KIR-ligand recognition in patients after unrelated hematopoietic stem cell transplantation for malignant diseases.

Transplantation of HLA and/or KIR mismatched allogeneic hematopoietic stem cells can lead NK cells to different states of activation/inhibition or education/resetting and change anti-tumor immunosurveillance. In this study, we used molecular relapse monitoring to investigate a correlation between either missing ligand recognition or variation of the cognate iKIR-HLA pairs with clinical outcomes in patients with hematological malignancies requiring allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients (N = 418) with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), or lymphoma receiving T-cell repleted graft from HLA-matched or partly mismatched unrelated donors between 2012 and 2020 in our center were included in this study. Missing-ligand recognition was assessed through the presence or absence of recipients' HLA ligand for a particular inhibitory KIR (iKIR) exhibited by the donor. Inhibitory KIR-HLA pair number variation was defined by loss or gain of a new cognate pair of HLA-KIR within the new HLA environment of the recipient, compared with the donor's one. Considering the results of our research, we drew the following conclusions: (i) loss of iKIR-HLA cognate pair for C1, C2, and/or Bw4 groups led to significant deterioration of disease-free survival (DFS), molecular relapse, overall survival (OS) and non-relapse mortality (NRM) for patients undergoing allo-HSCT in the standard phase of the disease. This phenomenon was not observed in patients who underwent transplantation in advanced hematological cancer. (ii) The missing ligand recognition had no impact if the proportion of HLA mismatches was not considered; however, adjustments of HLA mismatch level in the compared groups highlighted the adverse effect of the missing ligand constellation. (iii) The adverse effect of adjusted missing ligand suggests a predominance of lost NK cell education over lost NK cell inhibition in posttransplant recipients' new HLA environment. Our results suggested that donors with the loss of an iKIR-HLA cognate pair after transplantation should be avoided, and donors who provided an additional iKIR-HLA cognate pair should be preferred in the allo-HSCT donor selection process.

Bioethanol production from sorghum grain with Zymomonas mobilis: increasing the yield and quality of raw distillates.

BACKGROUND: The present study aimed to demonstrate the superiority of bioethanol yield and its quality from sorghum using the granular starch degrading enzyme Stargen™ 002 over simultaneous saccharification and fermentation, and separate hydrolysis and fermentation using Zymomonas mobilis CCM 3881 and Ethanol Red® yeast. RESULTS: Bacteria were found to produce ethanol at higher yield than the yeast in all fermentations. The highest ethanol yield was obtained with Z. mobilis during 48 h of simultaneous saccharification and fermentation (83.85% theoretical yield) and fermentation with Stargen™ 002 (81.27% theoretical yield). Pre-liquefaction in fermentation with Stargen™ 002 did not improve ethanol yields for both Z. mobilis and Saccharomyces cerevisiae. Chromatographic analysis showed twice less total volatile compounds in distillates obtained after bacterial (3.29-5.54 g L-1 ) than after yeast (7.84-9.75 g L-1 ) fermentations. Distillates obtained after bacterial fermentation were characterized by high level of aldehydes (up to 65% of total volatiles) and distillates obtained after yeast fermentation of higher alcohols (up to 95% of total volatiles). The process of fermentation using granular starch hydrolyzing enzyme cocktail Stargen™ 002 resulted in low amounts of all volatile compounds in distillates obtained after bacterial fermentation, but the highest amounts in distillates obtained after yeast fermentation. CONCLUSION: The present study emphasizes the great potential of bioethanol production from sorghum with Z. mobilis using granular starch hydrolyzing enzyme Stargen™ 002, which leads to reduced water and energy consumption, especially when energy sources are strongly related to global climate change. © 2023 Society of Chemical Industry.

Antiviral prophylaxis, male sex, and killer immunoglobulin-like receptor KIR2DL3 as markers for stratifying the risk of BK polyomavirus-associated nephropathy in kidney transplant recipients.

INTRODUCTION: The risk of polyomavirus­associated nephropathy (PyVAN) currently ranges from 1% to 10%, and the risk of graft loss is 10% to 50% within 2 years post­diagnosis. There is currently no specific antiviral therapy against BK polyomavirus (BKPyV), and no therapeutic approach has been proven superior. Natural killer cells play a key role in the defense against viral infections. OBJECTIVES: A retrospective, single­center cohort study was performed to investigate the association between the kidney transplant recipients' killer­cell immunoglobulin­like receptor (KIR) genotype and PyVAN. We also evaluated other possible risk factors for the occurrence of PyVAN in a population of kidney transplant recipients. PATIENTS AND METHODS: DNA samples from 134 kidney transplant recipients were identified for the presence or absence of variable KIR genes and their HLA ligands using polymerase chain reaction with sequence­specific primers. RESULTS: The analysis revealed that the presence of the inhibitory KIR2DL3 (P = 0.03) was a risk factor for posttransplant PyVAN. We also found that the presence of acute rejection before PyVAN (P = 0.02), male sex (P = 0.04), and the lack of antiviral prophylaxis (P = 0.01) were additional risk factors for posttransplant PyVAN. CONCLUSIONS: Our findings confirm that the KIR/HLA genotype plays a significant role in the development of PyVAN and suggest the contribution of both environmental and genetic factors to the incidence of BKPyV infection after kidney transplantation.

Paroxysmal nocturnal hemoglobinuria: advances in the understanding of pathophysiology, diagnosis, and treatment.

In recent years, "old" paroxysmal nocturnal hemoglobinuria (PNH) has achieved new advances in terms of the understanding of its pathophysiology, modern approach to diagnostics, optimization of therapy, and dynamic development of new therapeutic agents. This review emphasizes the greater than previously recognized importance of the reduced susceptibility of PNH stem cells to apoptosis in the selection of a defective clone. Some changes in cytokine and chemokine profiles in patients with PNH have been interpreted in the context of autoimmunity and apoptosis. The classification of PNH presentations, characteristics of the functions of selected glycosylphosphatidylinositol-anchored proteins, as well as pathologies associated with hemolysis, thrombosis, and bone marrow failure are described. The current diagnostic process for various forms of PNH is presented in detail, as well as its importance in the choice of treatment and prognosis of the disease course. Determinants of modern treatment, such as strategies (complement C5 inhibitors vs hematopoietic stem cell allotransplantation), the safety and efficacy of treatment with eculizumab or ravulizumab, policy of initiation and monitoring of treatment, the criteria for response to treatment and final outcomes of treatment are described. Among the new therapeutic agents, crovalimab and C5 inhibitors at a less advanced stage of research are discussed: tesidolumab, pozelimab, zilucoplan, nomacopan, and cemdisiran. The first approved proximal complement pathway inhibitors that primarily prevent extravascular hemolysis, pegcetacoplan, danikopan, and iptacopan, are presented and their potential benefits are highlighted.

The transient Spt4-Spt5 complex as an upstream regulator of non-coding RNAs during development.

The Spt4-Spt5 complex is conserved and essential RNA polymerase elongation factor. To investigate the role of the Spt4-Spt5 complex in non-coding transcription during development, we used the unicellular model Paramecium tetraurelia. In this organism harboring both germline and somatic nuclei, massive transcription of the entire germline genome takes place during meiosis. This phenomenon starts a series of events mediated by different classes of non-coding RNAs that control developmentally programmed DNA elimination. We focused our study on Spt4, a small zinc-finger protein encoded in P. tetraurelia by two genes expressed constitutively and two genes expressed during meiosis. SPT4 genes are not essential in vegetative growth, but they are indispensable for sexual reproduction, even though genes from both expression families show functional redundancy. Silencing of the SPT4 genes resulted in the absence of double-stranded ncRNAs and reduced levels of scnRNAs - 25 nt-long sRNAs produced from these double-stranded precursors in the germline nucleus. Moreover, we observed that the presence of a germline-specific Spt4-Spt5m complex is necessary for transfer of the scnRNA-binding PIWI protein between the germline and somatic nucleus. Our study establishes that Spt4, together with Spt5m, is essential for expression of the germline genome and necessary for developmental genome rearrangements.

Unexpected Relationships: Periodontal Diseases: Atherosclerosis-Plaque Destabilization? From the Teeth to a Coronary Event.

Atherosclerotic cardiovascular disease (ASCVD) and periodontal disease (PD) are global health problems. High frequency of ASCVD is associated with the spread of many risk factors, including poor diet, sedentary lifestyle, diabetes, hyperlipidemia, obesity, smoking, hypertension, chronic kidney disease, hypertension, hyperhomocysteinemia, hyperuricemia, excessive stress, virus infection, genetic predisposition, etc. The pathogenesis of ASCVD is complex, while inflammation plays an important role. PD is a chronic, multifactorial inflammatory disease caused by dysbiosis of the oral microbiota, causing the progressive destruction of the bone and periodontal tissues surrounding the teeth. The main etiological factor of PD is the bacteria, which are capable of activating the immune response of the host inducing an inflammatory response. PD is associated with a mixed microbiota, with the evident predominance of anaerobic bacteria and microaerophilic. The "red complex" is an aggregate of three oral bacteria: Tannerella forsythia Treponema denticola and Porphyromonas gingivalis responsible for severe clinical manifestation of PD. ASCVD and PD share a number of risk factors, and it is difficult to establish a causal relationship between these diseases. The influence of PD on ASCVD should be treated as a factor increasing the risk of atherosclerotic plaque destabilization and cardiovascular events. The results of observational studies indicate that PD significantly increases the risk of ASCVD. In interventional studies, PD treatment was found to have a beneficial effect in the prevention and control of ASCVD. This comprehensive review summarizes the current knowledge of the relationship between PD and ASCVD.

Persistent imbalance, anti-apoptotic, and anti-inflammatory signature of circulating C-C chemokines and cytokines in patients with paroxysmal nocturnal hemoglobinuria.

OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal non-malignant disease in which hematopoietic cell apoptosis may play an important pathophysiological role. Previous studies of the content of phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) indicated the possibility of remote transmission of anti-apoptotic signals between pathological and normal hematopoietic progenitors. METHODS: The study determined the plasma levels of beta chemokines and cytokines in N = 19 patients with PNH and 31 healthy controls. The research material was peripheral blood plasma (EDTA) stored at -80 °C until the test. Beta chemokine and cytokine concentrations were tested in duplicate with Bio-Plex Pro Human Cytokine Assay (Bio-Rad, Hercules, CA, USA) using a Luminex 200 flow cytometer and xPONENT software (Luminex Corporation, Austin, TX, USA). In peripheral blood CD34+ cells we tested the proportions of PI(3,4,5)P3+ and Annexin binding apoptotic phenotype using FC and phosflow. RESULTS: Compared to the control group, the PNH group showed a significant increase in the plasma concentration of some beta chemokines and cytokines, including MIP-1alpha/CCL3, eotaxin/CCL11, MCP1/CCL2, IL4 and G-CSF. In the group of PNH patients, a significant decrease in the concentration of some cytokines was also observed: RANTES/CCL5, MIP-1beta/CCL4, PDGF-BB and IL9. At the same time, the plasma concentrations of the chemokine IP-10/CXCL10 and the cytokines IFN-gamma, TNF, IL6 and IL10 showed no significant deviations from the values for the control group. Anti-apoptotic phenotype and phosphatidylinositol (3,4,5)-trisphosphate content in PNH clone of CD34+ cells were associated with the level of CCL3 and negatively associated with CCL5, CCL4, PDGF-BB and IL9. CONCLUSIONS: This data suggest the existence of apoptotic and PI(3,4,5)P3 imbalance in PNH CD34+ cells driven by anti-apoptotic cytokine biosignature in PNH. Plasma cytokines and intracellular enzymes that regulate the phosphoinositide pathways may become a therapeutic target in PNH.

Assessment of the Effect of A-PRF Application during the Surgical Extraction of Third Molars on Healing and the Concentration of C-Reactive Protein.

Extraction procedures for mandibular third molars are performed all over the world every day. Local inflammation resulting from surgery, and the pain that patients experience, often make it impossible to take up daily life activities, such as work or sports. Growth and anti-inflammatory factors, located in the fibrin network, have a positive effect on tissue-healing processes and should also reduce local inflammation. Advanced platelet-rich fibrin (A-PRF) applied locally influences such processes as: angiogenesis, osteogenesis and collagenogenesis. It also affects mesenchymal cell lines and anti- and pro-inflammatory mediators. Due to the autologous origin of the material, their use in guide bone regeneration (GBR) is more and more widespread in dentistry. The results of previous studies indicate that the use of A-PRF in the treatment area significantly reduces postoperative pain, while the formation of edema is not affected. C-reactive protein (CRP), which is an acute phase protein, appears in the blood as a consequence of inflammation. Due to the dynamics of changes in concentration of CRP, it is a protein that is sufficiently sensitive and is used in studies to monitor the tissue healing process. The effect of A-PRF application on CRP concentrations, before and after surgery, has not been investigated yet. The study was conducted on 60 generally healthy patients. A faster decrease of CRP levels was shown in patients who used A-PRF after the procedure. Additionally, it accelerated healing and reduced the occurrence of a dry socket close to 0.

[Recurrent ventricular tachycardia as a cause of circulatory decompensation in the case of various comorbid diseases]. / Nawracajace czestoskurcze komorowe jako przyczyna dekompensacji ukladu krazenia w przypadku róznych chorób wspóltowarzyszacych.

Ventricular arrhythmias, including tachycardia and ventricular fibrillation are often a dangerous consequence other co-existing conditions in the phase of their destabilization. Causal and symptomatic treatment diseases such as: ischemic heart disease, cardiac insufficiency, hyperthyroidism, or cancer, can be effectively stabilized without necessity for the implantation of cardioverter-defibrillator (ICD). CASE REPORT: The 62-year-old patient was admitted to the cardiology department after a second episode of unconsciousness last week due to recurrent VT. Despite many diagnostic difficulties, the possibility of effective conservative treatment has been demonstrated.

Fluctuations of the elemental composition in the layers of mineral deposits formed on the elements of biogas engines.

The aim of the research was to compare the chemical composition and morphology of the surface of the backsheet growing on the metallic and surface substrate growing already on the prepared mineral substrate. Moreover the aim of this study was also to analyze the dispersion of chemical elements on the cross-sections of deposits formed on parts of landfill biogas-driven engines. The chemical composition of extreme layers of mineral deposits extracted from the engine piston and their cross-sections from four pistons and one head was examined by SEM-EDS. The bottom side showed a much smaller heterogeneity of the topography of the surface than the topside. The chemical composition of the deposit bottom side it primarily S (41%), Si (34%) and Al (17%). In the case of the top side, the dominated of Ca (52%) with a relatively high share of S (32%) and Si (14%). The presence of P and Mg it was also found, but only on the bottom side, and the share of Fe and Zn only on the top side. In the case of cross-sections, Ca, S and Si were the dominant elements. In general, there were higher Si participations in the zone of the bottom layer with a downward trend to the top sheet. The mass shares of S and Ca were lower in the zone of the bottom layer with the upward trend to the top sheet, also undergoing fluctuation.

Heavy Metals as a Factor Increasing the Functional Genetic Potential of Bacterial Community for Polycyclic Aromatic Hydrocarbon Biodegradation.

The bioremediation of areas contaminated with hydrocarbon compounds and heavy metals is challenging due to the synergistic toxic effects of these contaminants. On the other hand, the phenomenon of the induction of microbial secretion of exopolysaccharides (EPS) under the influence of heavy metals may contribute to affect the interaction between hydrophobic hydrocarbons and microbial cells, thus increasing the bioavailability of hydrophobic organic pollutants. The purpose of this study was to analyze the impact of heavy metals on the changes in the metapopulation structure of an environmental consortium, with particular emphasis on the number of copies of orthologous genes involved in exopolysaccharide synthesis pathways and the biodegradation of hydrocarbons. The results of the experiment confirmed that the presence of heavy metals at concentrations of 50 mg·L-1 and 150 mg·L-1 resulted in a decrease in the metabolic activity of the microbial consortium and its biodiversity. Despite this, an increase in the biological degradation rate of polycyclic aromatic hydrocarbons was noted of 17.9% and 16.9%, respectively. An assessment of the estimated number of genes crucial for EPS synthesis and biodegradation of polycyclic aromatic hydrocarbons confirmed the relationship between the activation of EPS synthesis pathways and polyaromatic hydrocarbon biodegradation pathways. It was established that microorganisms that belong to the Burkholderiales order are characterized by a high representation of the analyzed orthologs and high application potential in areas contaminated with heavy metals and hydrocarbons.

High-resolution allele frequencies for NGS based HLA-A, B, C, DQB1 and DRB1 typing of 23,595 bone marrow donors recruited for the Polish central potential unrelated bone marrow donor registry.

Next-generation sequencing (NGS)-based typings of HLA-A, B, C, DQB1 and DRB1 loci were performed from 2018 to 2019 in 23 595 newly recruited or re-typed adult potential bone marrow donors registered in Poltransplant Registry to characterize allele and haplotype frequencies of HLA system for loci important for hematopoietic stem cell transplantation. The donors were recruited for registry and not for any other purpose including controls in a disease association study. The population sample was collected in various regions of Poland including all voivodships. The data regarding the degree of relatedness among individuals in the sample were not collected. Typings were supported by public funds as a part of the Polish National Program for Transplant Medicine Development. HLA frequency data are available in the Allele Frequencies Net Database.

Epstein-Barr virus infections are strongly dependent on activating and inhibitory KIR-HLA pairs after T-cell replate unrelated hematopoietic stem cell transplantation, the principles, and method of pairing analysis.

Viral infections are the main cause of increased morbidity and mortality among recipients in allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells fight virally infected cells provided directional activation of cytotoxicity. In this study, we analyzed the role of receptor-ligand pairs that include inhibitory or activating killer cell immunoglobulin-like receptors (KIRs) with their HLA class I ligands in the course of viral infections. The paper also presents an algorithm that allows performing automated inhibitory (i) KIR:HLA pairing and rechecking in the clinical setting. The obtained results indicate a significant adverse roles of reduced number of iKIR:HLA pairs (40% vs 9%; odds ratio [OR] = 6.67; P = .0057; 95% confidence interval [CI] 1.74-25.62) and the presence of activating KIR:HLA pairs (15% vs 5%, OR = 3.58, P = .028, 95% CI 1.19-10.73) in EBV infections post HSCT.

Influence of fermentation by different microflora consortia on pulque and pulque bread properties.

BACKGROUND: Pulque bread is a traditional Mexican product obtained by fermentation using microflora present only in pulque. In this study, the possibility of creating a pulque microbial consortium under laboratory conditions and its applications were evaluated. A laboratory-made consortium was compared with a consortium originating in Mexico in bread and pulque production. They were tested in various growth medium systems: pulque made from agave sap and malt extract, Mexican wheat and rye pulque bread, and European wheat and rye bread. RESULTS: Depending on the growth medium, consortiums showed differing influence on many factors, such as specific volume, weight loss after baking, soluble proteins, and crust and crumb color. Indigenous starters increased sensorial acceptance of pulque and Mexican rye bread, decreased pH, and increased titratable acidity of the breads at the highest level whereas laboratory consortia improved sensory acceptance of wheat breads. The laboratory-prepared starter in some cases improved antiradical activity. All pulques received similar consumer evaluations. However, malt pulque was the least appreciated beverage. CONCLUSION: The results show the possibility of creating a pulque microbial consortium under laboratory conditions. Depending on the flour type and the breadmaking technique, the use of a particular microbial consortium allowed modification of certain physicochemical parameters. In conclusion, it is feasible to modify bread parameters to obtain features corresponding to consumer demands by using an appropriate microflora, pulque, or flour type. Moreover, this research describes, for the first time, the use of rye malt for pulque and rye flour for pulque bread preparation as raw materials. © 2019 Society of Chemical Industry.

KIR specificity and avidity of standard and unusual C1, C2, Bw4, Bw6 and A3/11 amino acid motifs at entire HLA:KIR interface between NK and target cells, the functional and evolutionary classification of HLA class I molecules.

Natural killer (NK) cells make vital contributions to the immune system and the reproductive system. Notably, NK cells of donor origin can recognize and kill residual leukaemic cells and cure malignant patients in hematopoietic stem cell (HSC) transplant setting. NK cell function is regulated by KIRs that recognize cognate HLA class I molecules on target cells, depending on their amino acid residues. In review, we addressed the question of binding capacity and avidity of HLA class I molecules to different killer cell immunoglobulin-like receptors (KIRs) depending on all interacting amino acid residues both on HLA and KIR side. We searched PubMed database and analysed available HLA:KIR crystallographic data for amino acid residues in HLA molecules, those physically involved in binding KIRs (termed here the "entire KIR interface"). Within entire KIR interface, we selected five functional sequence motifs (14-19, 66-76, 77-84, 88-92 and 142-151) and classified them according to the conservation of their amino acid sequences among 8,942 HLA class I molecules. Although some conserved amino acid motifs were shared by different groups of KIR ligands, the HLA motif combinations were exclusive for the ligand groups. In 135 common HLA class I molecules with known HLA:KIR recognition, we found 54 combinations of five motifs in each of the KIR-binding interfaces (C1, C2, Bw4, A3/11) and conserved non-KIR-binding interfaces. Based on the entire KIR interface, this analysis allowed to classify 8,942 HLA class I molecules into KIR specificity groups. This functional and evolutionary classification of entire KIR interfaces provides a tool for unambiguously predicting HLA:KIR interactions for common and those HLA molecules that have not yet been functionally tested. Considering the entire KIR interface in HLA class I molecules, functional interactions of HLA and KIR can be predicted in immune responses, reproduction and allotransplantation. Further functional studies are needed on the HLA:KIR interaction variations caused by the repertoires of peptides presented by HLA molecules and KIR polymorphisms at allelic level.

Development of a Sustainable, Simple, and Robust Method for Efficient l-DOPA Extraction.

l-3,4-dihydroxyphenylalanine (l-DOPA) is a medically relevant compound in Parkinson's disease therapy. Several extraction methods of l-DOPA from beans, including velvet and faba beans, have been described in the literature. However, these methods require the use of strong acids, long extraction times, or complex downstream processing, which makes the extraction of l-DOPA expensive and energy-demanding, limiting its industrial application. In addition, the stability of l-DOPA during the extraction process is critical, further complicating the extraction of adequate amounts of this amino acid. This work is the first report on a simple, rapid, greener, and robust extraction method of l-DOPA. The developed method consists of a quick homogenization step followed by a double extraction with 0.2% v/v acetic acid for 20 min and was applied to faba bean at a ratio of 1:25 with respect to the extracting solvent. This study also investigated the stability of l-DOPA during extraction and thermal treatment. The proposed method demonstrated to be robust and extraordinarily efficient for numerous cultivars of faba bean, velvet bean, and food products containing faba beans.

Killer Immunoglobulin-Like Receptor 2DS2 (KIR2DS2), KIR2DL2-HLA-C1, and KIR2DL3 as Genetic Markers for Stratifying the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients.

Infection with cytomegalovirus (CMV) remains a major problem in kidney transplant recipients, resulting in serious infectious complications and occasionally mortality. Accumulating evidence indicates that natural killer cell immunoglobulin-like receptors (KIRs) and their ligands affect the susceptibility to various diseases, including viral infections (e.g., CMV infection). We investigated whether KIR genes and their ligands affect the occurrence of CMV infection in a group of 138 kidney transplant recipients who were observed for 720 days posttransplantation. We typed the recipients for the presence of KIR genes (human leukocyte antigen C1 [HLA-C1], HLA-C2, HLA-A, HLA-B, and HLA-DR1) by polymerase chain reaction with sequence-specific primers. The multivariate analysis revealed that the lack of KIR2DS2 (p = 0.035), the presence of KIR2DL3 (p = 0.075), and the presence of KIR2DL2⁻HLA-C1 (p = 0.044) were risk factors for posttransplant CMV infection. We also found that a lower estimated glomerular filtration rate (p = 0.036), an earlier time of antiviral prophylaxis initiation (p = 0.025), lymphocytopenia (p = 0.012), and pretransplant serostatus (donor-positive/recipient-negative; p = 0.042) were independent risk factors for posttransplant CMV infection. In conclusion, our findings confirm that the KIR/HLA genotype plays a significant role in anti-CMV immunity and suggest the contribution of both environmental and genetic factors to the incidence of CMV infection after kidney transplantation.

Effects of Different Techniques of Malolactic Fermentation Induction on Diacetyl Metabolism and Biosynthesis of Selected Aromatic Esters in Cool-Climate Grape Wines.

The effects of different malolactic bacteria fermentation techniques on the bioconversion of aromatic compounds in cool-climate grape wines were examined. During three wine seasons, red and white grape wines were produced using various malolactic fermentation induction techniques: Coinoculation, sequential inoculation, and spontaneous process. Volatile compounds (diacetyl and the products of its metabolism, and selected ethyl fatty acid esters) were extracted by solid phase microextraction. Compounds were identified with a multidimensional gas chromatograph-GC × GC-ToFMS with ZOEX cryogenic (N2) modulator. Sensory evaluation of the wines was also performed. It was found that the fermentation-derived metabolites studied were affected by the malolactic bacteria inoculation regime. Quantitatively, ethyl lactate, diethyl succinate, and ethyl acetate dominated as esters with the largest increase in content. The total concentration of ethyl esters was highest for the coinoculation technique, while the highest concentration of diacetyl was noted for the spontaneous technique. Controlled malolactic fermentation, especially using the coinoculation technique, can be proposed as a safe and efficient enological practice for producing quality cool-climate grape wines enriched with fruity, fresh, and floral aromas.

Role of donor HLA class I mismatch, KIR-ligand mismatch and HLA:KIR pairings in hematological malignancy relapse after unrelated hematopoietic stem cell transplantation.

HLA are functional in cancer immunosurveillance in adaptive and innate immunity pathways. In unrelated hematopoietic stem cell transplantation (HSCT) in 688 patients with hematological malignancies we compared antitumor efficacy of transplant in three models including the level of: (a) donor-recipient HLA class I mismatch, (b) KIR-ligand mismatch, (c) post-transplant cognate HLA:KIR pairing. The effects were directly compared in multivariate models with backward elimination including all three effects in initial model. In final multivariate model HLA mismatch and KIR-ligand mismatch levels were eliminated and HLA:KIR-dependent NK cell licensing effect remained independent prognostic factor for DFS, relapse/progression incidence, and overall survival (OS). These results suggested that NK cell licensing via cognate HLA:KIR pairs is primarily functional in cancer immunosurveillance in HSCT.

Effect of Replacing Cocoa Powder by Carob Powder in the Muffins on Sensory and Physicochemical Properties.

The increasing demand for cocoa and search for ingredients rich in bioactive compounds encouraged us to investigate the possibility of replacing it by carob powder in the muffins containing soy beans, sesame oil and flaxseeds. There was 5% addition of carob or cocoa powder to the individual doughs. The muffins with the addition of carob were characterized by improved antiradical activity (by 36% - 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) method, by 83% - 2,2-diphenyl-1-picrylhydrazyl (DPPH) method), higher content of genistein (18%) and total phytosterols (17%) in the dry mass. The color differences in the carob muffins crusts were not perceptible by consumers (ΔE = 0.70 for crust, ΔE = 5.6 for crumb) and their taste was found to be less bitter and sweeter than the taste of cocoa muffins. Moreover, the addition of carob powder as well as cocoa powder resulted in good sensory quality. The high content of phytosterols, genistein and improved antiradical properties proved carob to be a source of bioactive compounds. The results show that carob powder may be used as valuable alternative muffin ingredient to cocoa.