Awareness of Pregnant Patients about Congenital Cytomegalovirus Infection-A Semi-Systematic Review.

Background: Cytomegalovirus (CMV) infection represents a major issue worldwide, since it constitutes the most common viral congenital infection, with a prevalence of 0.58% and 1-5% in developed and developing countries, respectively. According to recent studies, prenatal treatment significantly decreases the risk of vertical CMV transmission, and early intervention may even prevent the termination of pregnancy. This study aimed to investigate the level of awareness of CMV among pregnant patients through a semi-systematic review. Methods: We included all of the original articles investigating knowledge and awareness about CMV infection among pregnant women. Our research included the PubMed database. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, the Covidence system automatically guided us to screen the titles and/or abstracts, and then full-texts, followed by data extraction from the eligible studies. Results: We screened 764 studies altogether, with 13 studies included in this analysis. Knowledge about the existence of CMV infection risk varied between the articles, ranging from 11.4% in a study performed in Ireland to 60% reported in a study on the French population. Studies analyzing the impact of educational interventions on patients' knowledge about preventive measures reported significant improvement compared to their level of awareness before the intervention. Conclusions: Patients' awareness and knowledge about CMV seemed to be generally low or very low during the last decade before the development of effective secondary prevention methods. Educational interventions seem to be effective, and therefore their wide use could be of potential benefit. In the era of available secondary prevention of vertical transmission, it is crucial to concentrate the efforts of different stakeholders to increase the awareness of cCMV among pregnant women.

Kinase-impaired BTK mutations are susceptible to clinical-stage BTK and IKZF1/3 degrader NX-2127.

Increasing use of covalent and noncovalent inhibitors of Bruton's tyrosine kinase (BTK) has elucidated a series of acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance mutations in BTK with distinct enzymatic activities, including some that impair BTK enzymatic activity while imparting novel protein-protein interactions that sustain B cell receptor (BCR) signaling. Furthermore, we describe a clinical-stage BTK and IKZF1/3 degrader, NX-2127, that can bind and proteasomally degrade each mutant BTK proteoform, resulting in potent blockade of BCR signaling. Treatment of chronic lymphocytic leukemia with NX-2127 achieves >80% degradation of BTK in patients and demonstrates proof-of-concept therapeutic benefit. These data reveal an oncogenic scaffold function of mutant BTK that confers resistance across clinically approved BTK inhibitors but is overcome by BTK degradation in patients.

Relationship between the gut microbiome and endometriosis and its role in pathogenesis, diagnosis, and treatment: a systematic review.

Endometriosis is a chronic inflammatory disease affecting approximately 10% of women. It is defined as endometrial tissue outside of the uterus and produces a variety of symptoms including pelvic pain, dysmenorrhea, dyspareunia, and intermenstrual bleeding. Although several theories have been postulated regarding the pathogenesis of endometriosis, no theory has provided a complete explanation, therefore limiting our progress in diagnostic tools and management of endometriosis. Recently, much attention has been paid to the importance and role of the gut microbiome in endometriosis. As defined by Joshua Lederberg - microbiome is a set of the genome of microorganisms inhabiting a human body, including commensal, symbiotic and pathogenic microorganisms. The aim of this systematic review was to conduct a search in the Embase, Medline, and PubMed databases for literature from July 2013 to July 2023 regarding the relationship between the gut microbiome and endometriosis. 147 records were screened, of which 26 met the eligibility criteria, and 16 were included in this review. Our review concludes that patients with endometriosis show an altered gut microbiome, and that this has the potential to provide insight for pathogenesis, markers for diagnosis, as well as therapeutic options for treatment of endometriosis. Future research is necessary to confirm this and further investigate the relationship between the gut microbiome and endometriosis.

The effect of two anti-inflammatory dietary components, omega-3 and resveratrol, on endometriosis.

Endometriosis is an inflammatory condition defined by the presence of endometrial glands and stroma outside the uterine cavity. Given the substantial body of evidence supporting the role of inflammation in the pathophysiology of various chronic illnesses, the concept of an anti-inflammatory diet has garnered significant attention in recent research. Some nutrients, such as omega-3 fatty acids and resveratrol (RES), have demonstrated distinct anti-inflammatory properties. Therefore, the objective of this systematic review was to search the Embase, Medline, and PubMed databases for literature from August 2008 to August 2023 regarding the effects of two anti-inflammatory dietary components, omega-3 and RES, on endometriosis. A total of 215 records were identified, out of which 58 were screened, 23 met the eligibility criteria, and 19 were included in this review. The results of this systematic review indicate that EPA is suggested to have anti-inflammatory properties and may serve as a potential marker for illness severity. RES offers a range of advantages, including inflammation reduction, angiogenesis suppression, proliferation inhibition, and apoptosis induction. To validate these findings and assess their clinical relevance, future research and clinical trials are warranted.

Personalized embryo transfer (pET) guided by endometrial receptivity (ER) assessment - a possibility to increase effectiveness of IVF procedures. Review of available methods.

The continuous development of assisted reproductive techniques (ART) implies the search for solutions that could increase the effectiveness ofavailable methods. In the context of in vitro fertilization (IVF), a significant proportion of failures are due to unsuccessful embryo transfers. At this stage the most important issue is proper dialogue between implanting embryo and the maternal endometrium. Therefore, it seems justified to assess endometrial receptivity (ER), defined as the tissue's ability to accept an embryo to attach and invade into the mucosa. Window of implantation (WOI), is a certain period in which implantation of the properly developed embryo is possible. The cause of endometrial receptivity disorders is believed to be the disturbed expression of cytokines and endometrial surface proteins, the presence of which has been proven in commonly diagnosed diseases such as endometriosis or chronic endometritis. Despite many years of research on endometrial receptivity, the area of ​​diagnostic methods enabling clinical monitoring of ER still remains undeveloped. The aim of this study is to review the utility of selected markers and the available methods of ER assessment, ranging from noninvasive ultrasound, through endometrial fluid analysis, to genomic studies based on endometrial biopsy, in order to increase the effectiveness of IVF. Such an approach could potentially be a significant step towards personalizing medical procedures especially in patients diagnosed with repeated implantation failure (RIF).

A tumor microenvironment model of chronic lymphocytic leukemia enables drug sensitivity testing to guide precision medicine.

The microenvironment of chronic lymphocytic leukemia (CLL) cells in lymph nodes, spleen, and bone marrow provides survival, proliferation, and drug resistance signals. Therapies need to be effective in these compartments, and pre-clinical models of CLL that are used to test drug sensitivity must mimic the tumor microenvironment to reflect clinical responses. Ex vivo models have been developed that capture individual or multiple aspects of the CLL microenvironment, but they are not necessarily compatible with high-throughput drug screens. Here, we report on a model that has reasonable associated costs, can be handled in a regularly equipped cell lab, and is compatible with ex vivo functional assays including drug sensitivity screens. The CLL cells are cultured with fibroblasts that express the ligands APRIL, BAFF and CD40L for 24 h. The transient co-culture was shown to support survival of primary CLL cells for at least 13 days, and mimic in vivo drug resistance signals. Ex vivo sensitivity and resistance to the Bcl-2 antagonist venetoclax correlated with in vivo responses. The assay was used to identify treatment vulnerabilities and guide precision medicine for a patient with relapsed CLL. Taken together, the presented CLL microenvironment model enables clinical implementation of functional precision medicine in CLL.

The Acquisition of Complement-Dependent Cytotoxicity by the Type II Anti-CD20 Therapeutic Antibody Obinutuzumab.

Rituximab, a prototypic anti-CD20 mAb, and the third-generation anti-CD20 mAb obinutuzumab differ in their ability to activate the complement system. According to recent studies, this contrast stems from the architecture of the antigen-antibody complex formed by these two mAbs that facilitates (rituximab) or disables (obinutuzumab) further oligomerization, leading to engagement of the initial classical complement pathway component C1q. We examined whether a gain-of-function C2 variant that acts downstream of C1q and enforces the formation of complement convertase resistant to physiological decay can impact complement activation by obinutuzumab. Co-application of the C2 variant with obinutuzumab and human serum resulted in complement-dependent cytotoxicity equal to or higher than attainable for rituximab. This effect was observed either in serum or hirudin-anticoagulated whole blood. Long-term (24 h) overall cytotoxicity of obinutuzumab was improved in target cells of moderate sensitivity to complement but diminished in cells of low sensitivity. Our results demonstrate that the ability of complement activation of a given antibody is not ultimately determined at the stage of initial interactions with its target antigen but is modulable at later stages of the cascade and that the benefit of the acquisition of this new effector mechanism by obinutuzumab depends on the target cell characteristics.

Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia.

PURPOSE: PI3K inhibitors (PI3Ki) are approved for relapsed chronic lymphocytic leukemia (CLL). Although patients may show an initial response to these therapies, development of treatment intolerance or resistance remain clinical challenges. To overcome these, prediction of individual treatment responses based on actionable biomarkers is needed. Here, we characterized the activity and cellular effects of 10 PI3Ki and investigated whether functional analyses can identify treatment vulnerabilities in PI3Ki-refractory/intolerant CLL and stratify responders to PI3Ki. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cell samples (n = 51 in total) from treatment-naïve and PI3Ki-treated patients with CLL were studied. Cells were profiled against 10 PI3Ki and the Bcl-2 antagonist venetoclax. Cell signaling and immune phenotypes were analyzed by flow cytometry. Cell viability was monitored by detection of cleaved caspase-3 and the CellTiter-Glo assay. RESULTS: pan-PI3Kis were most effective at inhibiting PI3K signaling and cell viability, and showed activity in CLL cells from both treatment-naïve and idelalisib-refractory/intolerant patients. CLL cells from idelalisib-refractory/intolerant patients showed overall reduced protein phosphorylation levels. The pan-PI3Ki copanlisib, but not the p110δ inhibitor idelalisib, inhibited PI3K signaling in CD4+ and CD8+ T cells in addition to CD19+ B cells, but did not significantly affect T-cell numbers. Combination treatment with a PI3Ki and venetoclax resulted in synergistic induction of apoptosis. Analysis of drug sensitivities to 73 drug combinations and profiling of 31 proteins stratified responders to idelalisib and umbralisib, respectively. CONCLUSIONS: Our findings suggest novel treatment vulnerabilities in idelalisib-refractory/intolerant CLL, and indicate that ex vivo functional profiling may stratify PI3Ki responders.

In Silico Designed Gain-of-Function Variants of Complement C2 Support Cytocidal Activity of Anticancer Monoclonal Antibodies.

The molecular target for the classical complement pathway (CP) is defined by surface-bound immunoglobulins. Therefore, numerous anticancer monoclonal antibodies (mAbs) exploit the CP as their effector mechanism. Conversely, the alternative complement pathway (AP) is spontaneously induced on the host and microbial surfaces, but complement inhibitors on host cells prevent its downstream processing. Gain-of-function (GoF) mutations in the AP components that oppose physiological regulation directly predispose carriers to autoimmune/inflammatory diseases. Based on the homology between AP and CP components, we modified the CP component C2 so that it emulates the known pathogenic mutations in the AP component, factor B. By using tumor cell lines and patient-derived leukemic cells along with a set of clinically approved immunotherapeutics, we showed that the supplementation of serum with recombinant GoF C2 variants not only enhances the cytocidal effect of type I anti-CD20 mAbs rituximab and ofatumumab, but also lowers the threshold of mAbs necessary for the efficient lysis of tumor cells and efficiently exploits the leftovers of the drug accumulated in patients' sera after the previous infusion. Moreover, we demonstrate that GoF C2 acts in concert with other therapeutic mAbs, such as type II anti-CD20, anti-CD22, and anti-CD38 specimens, for overcoming cancer cells resistance to complement attack.

Nationwide Registry-Based Analysis of Infective Endocarditis Risk After Pulmonary Valve Replacement.

Background Infective endocarditis (IE) after pulmonary valve replacements in congenital heart disease is a significant concern. This study aimed to identify specific long-term risk factors for IE after percutaneous pulmonary valve implantation or surgical pulmonary valve replacement. Methods and Results All patients with congenital heart disease from the National Register for Congenital Heart Defects with at least 1 pulmonary valve replacement before January 2018 were included. A total of 1170 patients (56.3% men, median age at study inclusion 12 [interquartile range {Q1-Q3} 5-20 years]) received 1598 pulmonary valve replacements. IE occurred in 4.8% of patients during a follow-up of total 9397 patient-years (median 10 [Q1-Q3, 6-10] years per patient). After homograft implantation 7 of 558 (1.3%) patients developed IE, after heterograft implantation 31 of 723 (4.3%) patients, and after Melody valve implantation 18 of 241 (7.5%) patients. Edwards Sapien and mechanical valves were used less frequently and remained without IE. The incidence of IE in heterografts excluding Contegra valves was 7 of 278 (2.5%), whereas the incidence of IE in Contegra valves was 24 of 445 (5.4%). The risk of IE was not increased compared with homografts if Contegra valves were excluded from the heterografts (hazard ratio [HR], 2.60; P=0.075). The risk of IE was increased for bovine jugular vein valves, Contegra valves (HR, 6.72; P<0.001), and Melody valves (HR, 5.49; P<0.001), but did not differ between Melody valves and Contegra valves (HR, 1.01; P=0.978). Conclusions Bovine jugular vein valves have the highest risk of IE, irrespective of the mode of deployment, either surgical or percutaneous.

Substitutions at position 263 within the von Willebrand factor type A domain determine the functionality of complement C2 protein.

The complement system is one of the first defense lines protecting from invading pathogens. However, it may turn offensive to the body's own cells and tissues when deregulated by the presence of rare genetic variants that impair physiological regulation and/or provoke abnormal activity of key enzymatic components. Factor B and complement C2 are examples of paralogs engaged in the alternative and classical/lectin complement pathway, respectively. Pathogenic mutations in the von Willebrand factor A domain (vWA) of FB have been known for years. Despite substantial homology between two proteins and the demonstration that certain substitutions in FB translated to C2 result in analogous phenotype, there was a limited number of reports on pathogenic C2 variants in patients. Recently, we studied a cohort of patients suffering from rare kidney diseases and confirmed the existence of two gain-of-function and three loss-of-function mutations within the C2 gene sequences coding for the vWA domain (amino acids 254-452) or nearly located unstructured region (243-253) of C2 protein. Herein, we report the functional consequences of amino acid substitution of glutamine at position 263. The p.Q263G variant resulted in the gain-of-function phenotype, similarly to a homologous mutation p.D279G in FB. Conversely, the p.Q263P variant found in a patient with C3 glomerulopathy resulted in the loss of C2 function. Our results confirm that the N-terminal part of the vWA domain is a hot spot crucial for the complement C2 function.

Pulmonary valve prostheses: patient's lifetime procedure load and durability. Evaluation of the German National Register for Congenital Heart Defects.

OBJECTIVES: We evaluated 4384 procedures performed between 1957 and 2018, collected in the National Register for Congenital Heart Defects, conducted on 997 patients with 1823 pulmonary valve replacements (PVRs), including 226 implanted via catheter [transcatheter valve (TCV)]. Main study targets are as follows: TCV benefit, valve type durability, decade-wise treatment changes and procedure frequencies over the lifetime of a PVR patient. METHODS: We studied TCV impact on surgical valve replacement (via Kaplan-Meier); pulmonary valve type-specific performance (Kaplan-Meier and Cox regressions with age group as stratification or ordinary variable); procedure interval changes over the decades (Kaplan-Meier); procedure load, i.e. frequency of any procedure/surgical PVR/interventional or surgical PVR by patient age (multistate analyses). RESULTS: TCV performance was equivalent to surgical PVRs and extended durability significantly. Homografts were most durable; Contegras lasted comparably less in older; and Hancock devices lasted less in younger patients. Matrix P-valves showed poorer performance. Age group stratification improves the precision of valve-specific explantation hazard estimations. The current median interval between procedures is 2.6 years; it became significantly shorter in most age groups below 40 years. At 30 years, 80% of patients had undergone ≥3 procedures, 20% ≥3 surgical PVRs and 42% ≥3 surgical or interventional PVRs. CONCLUSIONS: TCVs doubled freedom from explantation of conventional valves. Homografts' age group-specific explantation hazard ratio was lowest; Matrix P's hazard ratio was highest. Age-stratified Cox regressions improve the precision of prosthesis durability evaluations. The median time between procedures for PVR patients shortened significantly to 2.6 years. At 30 years, 42% had ≥3 PVRs.

The role of alternative electron pathways in the photosynthetic chain in higher plants / Rola alternatywnych sciezek przeplywu elektronów w lancuchu fotosyntetycznym roslin wyzszych.

Light-dependent reactions of photosynthesis takes place in the thylakoids of chloroplasts where light energy harvested from the sun drives the synthesis of ATP and NADPH. The major pathway of photosynthetic chain is the linear electron transport (LET), in which both photosystems (PSI and PSII) are involved, and ATP and NADPH are produced. However, ratio in production of those components is insufficient to cover the Calvin cycle energy requirements, depending on the metabolism of the cell. Moreover, disturbance in metabolism homeostasis, caused by environmental stress conditions, increases ATP demand, which cannot be covered by LET. Thus, in photosynthetic apparatus must exist alternative electron transport pathways, these include: cyclic electron transport (CET) mediated by NDH complex or PGR5/PGRL1 proteins, water-water cycle and PTOX enzyme. Activity of alternative pathways can optimize ratio in production of ATP/NADPH, appropriately to requirements, which allows to achieve redox balance and ATP contents.

Gain-of-Function Mutations R249C and S250C in Complement C2 Protein Increase C3 Deposition in the Presence of C-Reactive Protein.

The impairment of the alternative complement pathway contributes to rare kidney diseases such as atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). We recently described an aHUS patient carrying an exceptional gain-of-function (GoF) mutation (S250C) in the classical complement pathway component C2 leading to the formation of hyperactive classical convertases. We now report the identification of the same mutation and another C2 GoF mutation R249C in two other patients with a glomerulopathy of uncertain etiology. Both mutations stabilize the classical C3 convertases by a similar mechanism. The presence of R249C and S250C variants in serum increases complement-dependent cytotoxicity (CDC) in antibody-sensitized human cells and elevates deposition of C3 on ELISA plates coated with C-reactive protein (CRP), as well as on the surface of glomerular endothelial cells. Our data justify the inclusion of classical pathway genes in the genetic analysis of patients suspected of complement-driven renal disorders. Also, we point out CRP as a potential antibody-independent trigger capable of driving excessive complement activation in carriers of the GoF mutations in complement C2.

Light as a substrate: migration of LHCII antennas in extended Michaelis-Menten model for PSI kinetics.

We extended, for the first time, the Michaelis-Menten (M-M) model to describe the kinetics of photosystem I (PSI) complexes using light as a substrate. Our work is novel as it can be useful for studying the phenomenon of "state transitions" because it quantifies the affinity of light to PSI reaction centers depending on the associated light harvesting complex II (LHCII) antennas. We verified our models by measuring the PSI activity as a function of light intensity using an oxygen electrode for chloroplast from plants grown in low light conditions and treated with far red light. We determined the kinetics constant KM for: PSI-LHCI, PSI-LHCI-LHCII and PSI-PSII megacomplexes and have shown that KM for PSI located in the megacomplexes was smaller in magnitude than PSI-LHCI, thus demonstrating that LHCII antennas are functionally associated with PSI. The parameter [S]1/2used in our models is the equivalent of M-M constant. Far red light increases [S]1/2, which indicates that transition from state 1 to state 2 leads to an energy gain while reaching the PSI reaction centers. We also observed that redistribution of the absorbed excitation energy is realized not only by LHCII migration but also by association of the photosystems in the megacomplexes.

Two successful pregnancies after in vitro fertilisation with oocyte donation in a patient with Swyer syndrome - a case report.

Diagnosis of complete XY gonadal dysgenesis exposes the patient to the prospect of infertility and many years of medical treatment in order to avoid the development of diseases associated with this condition. However, sufficiently early diagnosis followed by the implementation of proper therapy improves the prognosis for enabling future pregnancies after IVF through the development of reproductive organs and prevention of health complications of hypoestrogenism such as cardiovascular problems and osteoporosis. This syndrome is very rare and affects 1 in 80,000 women. Due to the high risk of developing a gonadal tumour, prophylactic bilateral gonadectomy is one of the main procedures performed in a relatively brief time after diagnosis. Unfortunately, despite characteristic symptoms like primary amenorrhoea and underdeveloped breasts, the diagnosis is often made quite late. We report the case of a 45-year-old woman who had been diagnosed with Swyer syndrome at the age of 16 years. The patient underwent bilateral gonadectomy one year after the diagnosis due to the associated risk of developing malignancy and was treated since with hormone replacement therapy. At the age of 32 and 34 years, 2 successful IVF procedures were performed with oocyte donations. The pregnancies proceeded without any complications and both were resolved by caesarean section. The healthy sons' weights were 3600 g and 3700 g, respectively.

Understanding Maize Response to Nitrogen Limitation in Different Light Conditions for the Improvement of Photosynthesis.

The photosynthetic capacity of leaves is determined by their content of nitrogen (N). Nitrogen involved in photosynthesis is divided between soluble proteins and thylakoid membrane proteins. In C4 plants, the photosynthetic apparatus is partitioned between two cell types: mesophyll cells and bundle sheath. The enzymes involved in the C4 carbon cycle and assimilation of nitrogen are localized in a cell-specific manner. Although intracellular distribution of enzymes of N and carbon assimilation is variable, little is known about the physiological consequences of this distribution caused by light changes. Light intensity and nitrogen concentration influence content of nitrates in leaves and can induce activity of the main enzymes involved in N metabolism, and changes that reduce the photosynthesis rate also reduce photosynthetic N use efficiency. In this review, we wish to highlight and discuss how/whether light intensity can improve photosynthesis in maize during nitrogen limitation. We described the general regulation of changes in the main photosynthetic and nitrogen metabolism enzymes, their quantity and localization, thylakoid protein abundance, intracellular transport of organic acids as well as specific features connected with C4 photosynthesis, and addressed the major open questions related to N metabolism and effects of light on photosynthesis in C4 plants.

How to avoid drug resistance during treatment and prevention of urinary tract infections.

Urinary tract infections (UTIs), defined as the presence of bacteria above the bladder sphincter, are among the most common infectious diseases. They remain a significant cause of antibiotic prescription worldwide. The incidence is much higher among women, especially of reproductive age, than among men. If the infection occurs at least 3 times a year or twice within 6 months, it is classified as recurrent urinary tract infection (rUTI). Among the causal pathogens, the vast majority are Gram-negative bacteria, the most common of which is Escherichia coli. Recommended treatment regimens differ depending on the diagnosed disease entity and the patient's clinical situation. Empirical antibiotic therapy is most often used. The first-line treatment in patients with acute simple cystitis include nitrofurantoin, trimethoprim-sulfamethoxazole, or fosfomycin. Beta-lactams and fluoroquinolones should be considered as a second-line agent. In particular cases (pregnancy or rUTIs) targeted treatment, based on the results of urine culture and antibiogram, is implemented. During pregnancy recommended treatment includes administration of cephalosporins (e.g. cefuroxime) or nitrofurantoin. In patients with uncomplicated pyelonephritis fluoroquinolones should be considered as the first-line regimen. In the case of rUTIs, there are no uniform guidelines for prophylactic management. Repeated administration of antibiotics due to infections leads to a growing problem of drug resistance. Most recommendations suggest not to use antibiotic prophylaxis routinely. Growing evidence favours non-antibiotic prophylaxis regimens for recurrent UTIs. Until now only one product - oral immunostimulant OM-89 - has been sufficiently investigated. Wider implementation of immunoprophylaxis in the future may reduce possible side effects of inappropriate antibiotic consumption.

Monitoring of the Complement System Status in Patients With B-Cell Malignancies Treated With Rituximab.

Rituximab is a pioneering anti-CD20 monoclonal antibody that became the first-line drug used in immunotherapy of B-cell malignancies over the last twenty years. Rituximab activates the complement system in vitro, but there is an ongoing debate on the exact role of this effector mechanism in therapeutic effect. Results of both in vitro and in vivo studies are model-dependent and preclude clear clinical conclusions. Additional confounding factors like complement inhibition by tumor cells, loss of target antigen and complement depletion due to excessively applied immunotherapeutics, intrapersonal variability in the concentration of main complement components and differences in tumor burden all suggest that a personalized approach is the best strategy for optimization of rituximab dosage and therapeutic schedule. Herein we critically review the existing knowledge in support of such concept and present original data on markers of complement activation, complement consumption, and rituximab accumulation in plasma of patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphomas (NHL). The increase of markers such as C4d and terminal complement complex (TCC) suggest the strongest complement activation after the first administration of rituximab, but not indicative of clinical outcome in patients receiving rituximab in combination with chemotherapy. Both ELISA and complement-dependent cytotoxicity (CDC) functional assay showed that a substantial number of patients accumulate rituximab to the extent that consecutive infusions do not improve the cytotoxic capacity of their sera. Our data suggest that individual assessment of CDC activity and rituximab concentration in plasma may support clinicians' decisions on further drug infusions, or instead prescribing a therapy with anti-CD20 antibodies like obinutuzumab that more efficiently activate effector mechanisms other than complement.

Effect of light on the rearrangements of PSI super-and megacomplexes in the non-appressed thylakoid domains of maize mesophyll chloroplasts.

We demonstrated the existence of PSI-LHCI-LHCII-Lhcb4 supercomplexes and PSI-LHCI-PSII-LHCII megacomplexes in the stroma lamellae and grana margins of maize mesophyll chloroplasts; these complexes consist of different LHCII trimers and monomer antenna proteins per PSI photocentre. These complexes are formed in both low (LL) and high (HL) light growth conditions, but with different contents. We attempted to identify the components and structure of these complexes in maize chloroplasts isolated from the leaves of low and high light-grown plants after darkness and transition to far red (FR) light of high intensity. Exposition of plants from high and low light growth condition on FR light induces different rearrangements in the composition of super- and megacomplexes. During FR light exposure, in plants from LL, the PSI-LHCI-LHCII-Lhcb4 supercomplex dissociates into free LHCII-Lhcb4 and PSI-LHCI complexes, and these complexes associate with the PSII monomer. This process occurs differently in plants from HL. Exposition to FR light causes dissociation of both PSI-LHCI-LHCII-Lhcb4 supercomplexes and PSI-PSII megacomplexes. These results suggest a different function of super- and megacomplex organization than the classic state transitions model, which assumes that the movement of LHCII trimers in the thylakoid membraneis considered as a mechanism for balancing light absorption between the two photosystems in light stress. The behavior of the complexes described in this article does not seem to be well explained by this model, i.e., it does not seem likely that the primary purpose of these megacomplexes dynamics is to balance excitation pressure. Rather, as stated in this article, it seems to indicate a role of these complexes for PSI in excitation quenching and for PSII in turnover.