HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines

Eukaryotic genomes are transcribed into numerous regulatory long non-coding RNAs (lncRNAs). Compared to mRNAs, lncRNAs display higher developmental stage-, tissue-, and cell-subtype-specificity of expression, and are generally less abundant in a population of cells. Despite the progress in single-cell-focused research, the origins of low population-level expression of lncRNAs in homogeneous populations of cells are poorly understood. Here, we identify HIPSTR (Heterogeneously expressed from the Intronic Plus Strand of the TFAP2A-locus RNA), a novel lncRNA gene in the developmentally regulated TFAP2A locus. HIPSTR has evolutionarily conserved expression patterns, its promoter is most active in undifferentiated cells, and depletion of HIPSTR in HEK293 and in pluripotent H1BP cells predominantly affects the genes involved in early organismal development and cell differentiation. Most importantly, we find that HIPSTR is specifically induced and heterogeneously expressed in the 8-cell-stage human embryos during the major wave of embryonic genome activation. We systematically explore the phenomenon of cell-to-cell variation of gene expression and link it to low population-level expression of lncRNAs, showing that, similar to HIPSTR, the expression of thousands of lncRNAs is more highly heterogeneous than the expression of mRNAs in the individual, otherwise indistinguishable cells of totipotent human embryos, primordial germ cells, and stable cell lines

Elevated percentage of HLA-DR⁺ and ICAM-1⁺ conjunctival epithelial cells in active Graves' orbitopathy.

BACKGROUND: To evaluate if conjunctival epithelial cells' expression of HLA-DR and ICAM-1 could be helpful as early topical markers of inflammation in Graves' orbitopathy (GO). METHODS: The ocular examination evaluated a clinical activity score (CAS) by assessment of clinical features, (e.g., eyelid or conjunctival inflammation, lid width, lid closure, proptosis, ocular motility). Conjunctival epithelial cell specimens for flow-cytometric evaluations of ICAM-I and HLADR expression were collected by impression cytology from ten eyes with active GO (CAS ≥ 4 and duration ≤ 12 months), from 15 eyes with Graves' disease (GD) without active GO (CAS 0-2) and from 15 normal specimens without any ocular disorders. RESULTS: The percentage of HLA-DR + conjunctival epithelial cells was significantly elevated in patients with active GO comparing to GD without active GO and healthy controls, 10.7 % (8.5-17.7) and 7.78 % (3.92-10.1) (p < 0.05) vs. control 4.89 % (3.5-5.5) (p < 0.005), respectively. The expression of ICAM - 1+ conjunctival epithelial cells was greater only in patients with GO vs. controls, 5.5 % (4.8-7.03) and 1.46 % (0.69-2.51) (p < 0.005), respectively. CONCLUSION: The percentage of HLA-DR⁺ and ICAM-1⁺ conjunctival epithelial cells in patients with the active GO may serve as a topical inflammation marker in Graves' orbitopathy.

The progressive reduction in the ovarian reserve in young women after anticancer treatment.

Anticancer treatment can disturb gonadal function and deplete the primordial follicle pool, leading to premature menopause. We made a prospective analysis of serum hormone levels in young female cancer survivors who had been treated during childhood and adolescence. Serum anti-Müllerian hormone (AMH) as a marker of ovarian reserve, FSH, LH, and estradiol were measured in 33 women treated previously (6-11 years earlier) for Hodgkin Lymphoma, solid tumours, and after bone marrow transplantation, and in 34 healthy controls. The group of survivors was divided according to the risk of gonadotoxicity into the low risk and median risk group (LR+MR), and into the high risk (HR) group. The measurements were repeated after 5 years. In the HR group, AMH levels were significantly lower than in controls (p=0.001) and in the LR+MR group (p=0.006) at the time of the first examination fell progressively after 5 years (p=0.03), whereas elevated FSH values (p=0.053) increased (p=0.001). Unchanged LH values in the first measurement rose in the second one (p=0.001). In the LR+MR group, the levels of AMH and FSH were normal (compared to the control) at baseline, but after 5 years serum AMH decreased (p=0.027) and FSH increased (p=0.008). Our findings indicate that anticancer treatment during childhood and adolescence is associated with a serious, progressive risk of ovarian failure. It is necessary to inform female cancer survivors, especially the high risk patients, about the risk of premature menopause.

Sarcoidosis and tuberculosis: a connection to the human leukocyte antigen system.

Infectious, genetic factors, and autoimmunity have been considered as potential causes of sarcoidosis (SA). Pathological similarities between SA and tuberculosis (TB) suggest M. tuberculosis antigen(s) as causative agent(s). Our published comparative analysis of the human leukocyte antigens (HLA) system in patients with SA or TB in the same ethnic group revealed that some antigens were connected with high risk of developing of SA or TB, but other were comparable in both patient populations. Is it possible that the predominating occurrence of HLA antigens characteristic for TB may cause tuberculosis in patients with SA? To answer this question we evaluated the HLA class I and II alleles frequency by PCR amplification with sequence-specific primers in three women with histopathologically proven pulmonary SA, who developed bacteriologically confirmed TB on a corticosteroids (CS) therapy. Analysis of HLA in every case separately revealed a trend for higher occurrence of both alleles predisposing and protecting from TB than SA, in comparison with healthy individuals in our previously mentioned HLA genotyping study. Overall, the number of alleles predisposing to TB was statistically greater than the number of alleles connected with a high risk of developing SA. Also, the frequency of protecting alleles was statistically higher for TB than for SA. Therefore, SA in these patients developed at first, and the presence of additional environmental factors, e.g., age, CS might decrease an immune response and provoked TB. There is a possibility that the occurrence of HLA antigen more associated with high risk of developing TB than SA causes the development of tuberculosis in our patients with sarcoidosis.

Evaluation of the influence of ozonotherapy on the clinical parameters and MMP levels in patients with chronic and aggressive periodontitis.

PURPOSE: A comparison of the clinical status and salivary MMP levels after SRP alone or with ozonotherapy in patients with aggressive and chronic periodontitis. MATERIAL/METHODS: The study was performed in 52 generally healthy subjects with chronic or aggressive periodontitis. Group CP-S consisted of 12 patients with chronic periodontitis, who underwent scaling and root planing (SRP). In group CP-O there were 25 patients with chronic periodontitis who additionaly to SRP underwent ozonotherapy. The same therapy was performed in group AP, containing 15 patients with aggressive periodontitis. Plaque index, approximal plaque index, bleeding on probing, sulcus bleeding index, probing pocket depth and clinical attachment loss were measured at baseline, at two weeks and two months post-therapy. The levels of MMP-1, MMP-8 and MMP-9 were estimated in non-stimulated saliva with an ELISA method. RESULTS: All the clinical parameters assessed in the study groups were reduced after treatment. SRP with additional ozonotherapy provided an increase in MMP levels in patients with chronic periodontitis and a reduction in MMP levels in patients with aggressive periodontitis. CONCLUSIONS: SRP followed by ozonotherapy does not lead to further improvement in clinical periodontal parameters in patients with AP and CP.

Simple and rapid screening for HLA-Cw*06 in Polish patients with psoriasis.

BACKGROUND: The human leucocyte antigen (HLA) C allele Cw*06 is currently recognized as a major disease allele at the PSORS1 locus. It has been suggested that characterization of this gene could be used as a convenient criterion for classification of psoriasis phenotypes. AIM: To design and optimize a DNA typing procedure, suitable for identification of HLA-Cw*06 and its zygosity status verification in large-scale analyses, and to test for its robustness in a case-control study. METHODS: PCR assays with sequence-specific primers (PCR-SSP) were used for specific detection of HLA-Cw*06. PCR with analysis of restriction fragment length polymorphism was used to distinguish between patients homozygous and heterozygous for HLA-Cw*06. Additionally, those homozygous for HLA-Cw*06 were screened for nonspecific digestion by degenerated PCR-SSP. This three-step procedure was used in the examination of 383 patients with psoriasis that developed at the age of >or= 30 years of age and of 143 healthy subjects from northern Poland. RESULTS: A simple and rapid procedure for screening of HLA-Cw*06 was produced. A significant difference in HLA-Cw*06 frequency between patients with psoriasis and controls was seen (P = 0.02). Detailed examination of the age of disease onset among patients with psoriasis revealed that involvement of HLA-Cw*06 in the genetic background of psoriasis developing as late as the age of 45 years cannot be neglected. CONCLUSIONS: The low cost, high-throughput capacity and requirement for small sample amounts make this procedure a useful one for HLA-Cw*06 typing in clinical practice and large population studies. We recommend that patients with psoriasis diagnosed before 45 years of age should be considered for diagnostic HLA-Cw*06 typing.

Assessment of aprotinin influence on periodontal clinical status and matrix metalloproteinases 1, 2 and their tissue inhibitors saliva concentrations in patients with chronic periodontitis.

PURPOSE: Assessment of the effect of treatment with aprotinin-containing drug on the clinical status of the periodontal tissue and on the concentrations of metalloproteinases released in the course of periodontitis (MMP-1, MMP-2) as well as their tissue inhibitors (TIMP-1 and TIMP-2) in the saliva of patients with chronic periodontitis (CP). MATERIAL/METHODS: The study involved 25 subjects with CP (39-68 years), including 16 women and 9 men. The patients were prescribed aprotinin preparation to be taken for 2 weeks. The control group (C) involved 14 healthy subjects (41-65 years), including 10 women and 4 men. Two periodontal indices were assessed: the approximal plaque index (API) and bleeding on probing index (BOP). Periodontal pocket depth and clinical attachment level were also evaluated. The concentrations of MMP-1 and MMP-2 as well as TIMP-1 and TIMP-2 were determined by the ELISA method. RESULTS: The mean salivary MMP-1 concentration in patients with CP was significantly higher before and after treatment, as compared to healthy subjects. The mean salivary MMP-2 concentration in CP patients at baseline was also higher as compared to the C group and increased after treatment. The mean salivary TIMP-1 and TIMP-2 concentration in CP patients was higher as compared to C group and increased after treatment. CONCLUSIONS: Since the mean MMPs levels were found to be growing it can be assumed that aprotinin has no significant effect on the regulation of MMPs in the saliva of CP patients. It thus seems that aprotinin application after scaling has no additional therapeutic effect.

Expression of FasR, Fas-L and Bcl-2 in CD4+ and CD8+ subpopulations of T lymphocytes in the cord blood of healthy full-term newborns, is gender of influence?

PURPOSE: The expression of FasR, Fas-L and Bcl-2 on CD4+ and CD8+ T lymphocytes subpopulations from the cord blood were assayed. The results in blood from boys and girls were analyses separately and compared. MATERIAL AND METHODS: Twenty four full-term newborns: 13 females and 11 males were included into the study. Blood from the umbilical vein was collected immediately after cutting the umbilical cord. The staining with monoclonal antibodies against CD4, CD8, FasR, Fas-L and Bcl-2 was performed within 2 hours after collection and followed with flow cytometry acquisition and analysis. RESULTS: The percentage of CD4+ and CD8+ T lymphocytes and CD4+:CD8+ ratio was within normal range. The expression of FasR, Fas-L was higher on CD4+ T lymphocytes than on CD8+ T lymphocytes (10,36% vs 6,79% and 6,66% vs 5,63% respectively). The expression of Bcl-2 was comparable (91,9% and 93,75% respectively). The comparison between males and females showed higher percentage of CD4+ lymphocytes on lymphocytes from girls' blood (56% vs 38,69%, p=0.0003). The expression of FasR and Fas-L on CD4+ T lymphocytes was higher on CD4+ T lymphocytes from girls' blood (13,8% vs 7,53% and 6,8% vs 6,52% respectively) but without statistical significance. Bcl-2 expression was higher on CD4+ T lymphocytes from boys' blood (99,65% vs 89,7%) but without statistical significance. Similar pattern of FasR, Fas-L and Bcl-2 expression was noted on CD8+ T lymphocytes analysed separately for girls' and boys' blood origin cells. The difference in Bcl-2 expression was more prominent than on CD4+ T lymphocytes and reached statistical significance. CONCLUSIONS: The lymphocytes from cord blood of boys showed the more immature immunophenotype than T lymphocytes from cord blood of girls'. Impaired apoptosis (as a consequence of low expression of FasR, Fas-L) in neonatal cells may contribute to prolonged inflammation in newborns after oxidative stress or infection.

Flow cytometric analysis of HLA-DR antigen in conjunctival epithelial cells of patients with cystic fibrosis.

PURPOSE: Cystic fibrosis (CF) is an autosomal-recessive genetic disorder. The disease affects all secretory epithelia including the eye and belongs to the group of ocular surface epithelial diseases, termed keratoconjunctivitis sicca that develop in dry eye. In the pathogenesis of dry eye, inflammation plays a crucial role. The aim of this study was to investigate the expression of HLA-DR on conjunctival epithelial cells from patients with CF. MATERIALS AND METHODS: Twenty-five patients with CF and 25 normal subjects underwent ocular examination. Tear film break-up time (TBUT), Schirmer test, lissamine green staining, and conjunctival impression cytology were carried out. Cells were processed for flow cytometry, by using monoclonal antibodies to HLA-DR. RESULTS: The Schirmer test and TBUT scores were significantly lower in CF patients compared with controls. A significant increase of HLA-DR expression on epithelial cells was found in patients with CF compared with normal eyes. The Schirmer and TBUT test were positively correlated with HLA-DR expression for the percentage of cells. CONCLUSION: These results suggest that conjunctival epithelial cells play an important proinflammatory role in ocular changes in CF patients. Our findings confirm the presence of an inflammatory background and the immune nature of this disease. HLA-DR measurement might be a useful method for monitoring of inflammatory processes in the conjunctiva and could be helpful in the use of anti-inflammatory drugs in the treatment of ocular findings in CF patients.

Acute lymphoblastic leukaemia cells express CCR7 but not higher amounts of IL-10 after CD40 ligation.

OBJECTIVE: Production of cytokines that support T-cell activation and proliferation and migration to lymph nodes is one of the most important terms of cancer vaccine development. In previous studies we and others used CD40 ligation to obtain higher expression of co-stimulatory and adhesion molecules on leukaemic cells from children with acute lymphoblastic leukaemia (ALL). This time we assess the cytokine and chemokine gene expression profile in CD40-stimulated ALL cells. MATERIAL AND METHODS: Malignant cells from 25 children with BCP-ALL were stimulated (or not) with huCD40LT and rIL-4 for 96 h. Eleven different molecule, cytokine and chemokine mRNAs levels (CCR7, IL-23, TGF-beta-IP, IFN-gamma, IL-10, CD1a, CD40, CD54, CD80, CD83, CD86) were determined using the real-time PCR technique with TaqMan chemistry using ready-to-use low-density arrays for gene expression by Applied Biosystems. RESULTS: 1) Increases in mRNA levels for CD40, CD54 and CD80 after CD40L and IL-4 stimulation were observed, 2) CCR7 mRNA expression was higher after CD40 ligation than before the culture (p = 0.002), 3) IL-10 mRNA expression was higher after the culture with medium than before the culture (p = 0.01). CONCLUSIONS: The results show that leukaemia-derived dendritic cells obtained with CD40 ligation express CCR7 - chemokine is involved in migration to lymph nodes and does not produce higher amounts of IL-10, a potent immunosuppressive cytokine. Our preclinical findings could be used in the design of immunotherapy trials for the treatment of children with ALL.

Evaluation of mCD14 expression on monocytes and the blood level of sCD14 in patients with generalized aggressive periodontitis.

PURPOSE: Lipopolysaccharides (LPS), a major component of the cell membrane of gram-negative bacteria, are the main stimulants of the host immune response, initiating inflammatory changes and responsible for periodontal tissue destruction. The mCD14, which is found primarily on monocytes and macrophages, is the key membranous receptor involved in LPS binding. CD14 is also present in the serum as a soluble form (sCD14) released due to shedding from monocytes. The aim of the study was to assess CD14 expression on peripheral blood monocytes in patients with generalized aggressive periodontitis (GAP). The level of sCD14 was also determined in the serum of GAP patients. MATERIAL AND METHODS: The study group consisted of 16 patients with generalized aggressive periodontitis, the control group had 13 systemically and periodontally healthy subjects. The expression of mCD14 was determined by flow cytometry and expressed as mean intensity of fluorescence (MIF). Serum sCD14 level was examined with ELISA method. RESULTS: The expressions of mCD14 on monocytes in GAP patients and control subjects were comparable. No statistically significant differences were noted in the mean serum sCD14 level between GAP and control subjects. CONCLUSIONS: As periodontitis is a local disorder affecting a small fragment of the oral cavity it seems likely that chronic bacterial infection existing there is not reflected in the peripheral parameters.

Immature reticulocyte fraction (IRF)--an universal marker of hemopoiesis in children with cancer?

PURPOSE: Anemia is one of the most frequent side effects of anticancer treatment, it is also caused by disease itself. Reliable laboratory tests indicating hematological recovery after chemo- and radiotherapy are needed. Effective erythropoiesis can be monitored by quantitative measurement of reticulocytes. The amount of RNA in these cells can be assessed with flow cytometry and divided into low- (LFR), middle- (MFR) and high-fluorescence reticulocytes (HFR). This distribution is correlated with their maturation. MATERIAL AND METHODS: The aim of our study was to find the most sensitive indicator of anaemia among reticulocyte subpopulations assesed by flow cytometry in children with cancer. 46 children with different neoplasmatic diseases were enrolled into the study. RESULTS: 1) we did not find any differences between control and examined group at the time of diagnosis except for IRF, which was higher in examined group (p = 0.001); 2) IRF was lower already 2-4 days after end of chemotherapy (p = 0.03), and rised before next regimen (p = 0.0006). CONCLUSIONS: In conclusion we showed that IRF is not only the first sign of hematologic recovery but also very strong indicator of postchemotherapy aplasia in children with cancer and may serve as a additional parameter of bone marrow function in clinical studies.

Plasma fibrinogen concentration in pediatric patients treated with an elimination diet based on soy proteins and casein hydrolyzate.

PURPOSE: Fibrinogen is one of the most discussed new risk factors of atherosclerosis. The aim of the study was to assess the relationship between fibrinogen concentration and classic risk markers of atherosclerosis in a group of children aged from 2 to 6 with or without a family history of circulatory system diseases (FHCAD) (American Academy of Pediatrics--AAP criteria). The study also considered the impact of allergies/food intolerance treatment with elimination diets on the concentration of atherosclerosis markers specially fibrinogen. INCLUSION CRITERIA: a) family history of early occurrence of circulatory system diseases (FHCAD+) according to AAP standards; b) the type and duration of elimination diet continued in infancy and early childhood. 134 of 388 children were included in the investigation. RESULTS: The analysis of data relating to the so-called classic biochemical risk factors of atherosclerosis (total cholesterol--TC, HDL, LDL, triglycerides, glucose) did not reveal any differences between the tested groups. It was found that in the FHCAD+ group the concentration of fibrinogen was statistically higher than in the group with a negative family history. It was discovered that the type of elimination diet had no effect on fibrinogen level in the FHCAD+ group. In the group of children with negative family history the concentration of fibrinogen was statistically lower in the group on casein hydrolysate than in children treated with soy formula. CONCLUSIONS: The initial interview in pediatrics should include information on the patient's family history of atherosclerosis. In case of a positive family history, fibrinogen, as one of atherosclerosis risk factors, should be monitored.

Northern Polish population data and forensic usefulness of 15 autosomal STR loci.

Allele frequencies for the 15 STR loci in the AmpF/STR Identifiler kit (Applied Biosystems): D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818, and FGA were determined in a sample of 145 unrelated individuals living in the northern part of Poland. The values of heterozygosity, polymorphic information content (PIC), power of discrimination (PD), power of exclusion (PE), paternity index (PI) and matching probability (pM)were calculated.

[Lymphocyte subpopulations in the adenoids analyzed by flow cytometry]. / Ocena subpopulacji limfocytów w przeroslych migdalkach gardlowych metoda cytometrii przeplywowej.

Adenoid hypertrophy is a common problem of childhood. The peak occurrence of adenoid hypertrophy correlates with the onset of serous otitis media. The aim of the study was to evaluate the lymphocyte subpopulations in the adenoids of children with serous otitis media. The adenoids obtained from 65 children at the age of 1 to 17 years were examined. Two groups were studied: 1) children with persistent effusion in the middle ear, 2) children with adenoid hypertrophy without a history of otitis media. The percentage of the lymphocytes B in the adenoids was similar in both groups. However, the percentage of lymphocytes T (p < 0.04), and CD4+ (p < 0.005) was significantly lower in adenoids of children with serous otitis media. The percentage of lymphocytes T HLA-DR+ was slightly higher in this group, but the percentage of lymphocytes T CD25+ was the same in both groups. The quantitative differences in the lymphocyte subpopulations of adenoids may be the predisposing factor in serous otitis media.

Activation of blood platelets in chronic hepatitis and liver cirrhosis P-selectin expression on blood platelets and secretory activity of beta-thromboglobulin and platelet factor-4.

BACKGROUND/AIMS: Blood platelets are cells that quite often undergo damage in chronic liver diseases. Endotoxemia and hyperkinetic circulation influence platelets in an active manner. The role of platelets in the development of hepatitis and liver fibrosis is speculative. The aim of the study was to determine the influence of chronic liver diseases on platelets morphologic parameters, their secretory activity and P-selectin expression. METHODOLOGY: The examination was completed in the group of 29 patients with chronic hepatitis and 27 with liver cirrhosis of postinflammatory etiology (HBV, HCV). Liver biopsies were carried out in all patients. Thirty-two healthy individuals were the control group. Platelets morphological parameters (number, volume, platelet crit, micro- and macrothrombocyte fraction) were estimated. beta-thromboglobulin concentration and platelet factor 4 in blood serum as well as P-selectin expression on resting platelets and after thrombin activation were also examined. RESULTS: Number, volume, and platelet crit decreased with the advancement of a liver disease. Megathrombocyte fraction increased inversely with the severity of liver damage. The concentration of beta-thromboglobulin and platelet factor 4 alpha-granule contents in blood serum was higher 2- and 7-times, respectively than in healthy controls. P-selectin expression on resting platelets was considerably higher. After stimulation with thrombin, P-selectin expression was equal (chronic hepatitis) or higher (liver cirrhosis) than in the control. CONCLUSIONS: There are changes of platelet morphological parameters, with accompanying megathrombocyte fraction increase that occur in chronic liver diseases. Thrombocytes in chronic liver diseases and liver cirrhosis are more activated. Platelet sensitivity to stimuli in these ailments is higher (liver cirrhosis) than in the healthy controls.

Loss of HCF-1-chromatin association precedes temperature-induced growth arrest of tsBN67 cells.

Human HCF-1 is a large, highly conserved, and abundant nuclear protein that plays an important but unknown role in cell proliferation. It also plays a role in activation of herpes simplex virus immediate-early gene transcription by the viral regulatory protein VP16. A single proline-to-serine substitution in the HCF-1 VP16 interaction domain causes a temperature-induced arrest of cell proliferation in hamster tsBN67 cells and prevents transcriptional activation by VP16. We show here that HCF-1 is naturally bound to chromatin in uninfected cells through its VP16 interaction domain. HCF-1 is chromatin bound in tsBN67 cells at permissive temperature but dissociates from chromatin before tsBN67 cells stop proliferating at the nonpermissive temperature, suggesting that loss of HCF-1 chromatin association is the primary cause of the temperature-induced tsBN67 cell proliferation arrest. We propose that the role of HCF-1 in cell proliferation is to regulate gene transcription by associating with a multiplicity of DNA-bound transcription factors through its VP16 interaction domain.

Developmental and cell-cycle regulation of Caenorhabditis elegans HCF phosphorylation.

HCF-1 is a mammalian protein required for cell proliferation. It is also involved in transcriptional activation of herpes-simplex-virus immediate-early gene transcription in association with the viral transactivator VP16. HCF-1 and a related protein called HCF-2 possess a homologue in Caenorhabditis elegans that can associate with and activate VP16. Here, we demonstrate developmental regulation of C. elegans HCF (CeHCF) phosphorylation: a hyperphosphorylated form of CeHCF is present in embryos, whereas a hypophosphorylated form is present in L1 larvae. The phosphorylation patterns of endogenous CeHCF in worms and ectopically synthesized CeHCF in mammalian cells are remarkably similar, suggesting that the way CeHCF can be recognized by kinases is conserved in animals. Phosphorylation-site mapping of endogenous CeHCF, however, revealed that phosphorylation occurs at four clustered sites in the region of the protein that is not highly conserved among HCF proteins and is not required for VP16-induced complex formation. Indeed, phosphorylation of either CeHCF or human HCF-1 appears to be dispensable for association with VP16. All four CeHCF phosphorylation sites match the consensus recognition site for the cell-cycle kinases CDC2 and CDK2. Consistent with this similarity and with the developmental phosphorylation of CeHCF in C. elegans embryos, CeHCF phosphorylation is cell-cycle-regulated in mammalian cells.

[Granules of neutrophils]. / Ziarnistosci granulocytów obojetnochlonnych.

The exocytosis of cytoplasmic granules plays a most important role in the regulation of many neutrophils functions: adhesion, phagocytosis, killing of bacteria and interaction with endothelial cells. Neutrophils contain following types of granules: azurophilic (primary) granules, specific (secondary) granules, gelatinase-rich tertiary granules and secretory vesicles. Neutrophil granules may be classified on the basis of their size, morphology, density or with reference to a given protein.