CD15 (Lewis x) Expression in Human Myeloid Cell Differentiation Is Regulated by Sialidase Activity.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1931-1931
Author(s):  
Samah Z. Gadhoum ◽  
Robert Sackstein
Keyword(s):  
De Novo ◽  
Morphological Changes ◽  
Critical Role ◽  
Myeloid Cells ◽  
Granulocytic Differentiation ◽  
Induced Differentiation ◽  
Lewis X ◽  
Sialidase Activity ◽  
The Core ◽  
Sialyl Lex

Abstract The cell surface carbohydrate Lewis x (Lex, CD15) is now well established as an important marker for immunophenotyping leukocytes and for immunoregulatory functions. Lex is related to sialyl Lex (sLex) by the addition of a sialic acid in the core Lex trisaccharide. This sialylation has profound implications as it confers novel biological function(s) to the core trisaccharide. In particular, expression of sLex correlates with E-selectin ligand activity. Though the expression of Lex in myeloid differentiation is now widely recognized, no studies to date have addressed the molecular mechanism regulating its expression. To examine this issue, we employed a leukemic model of differentiation based on the capacity of anti-CD44 mAbs to induce maturation and Lex expression. We found that anti-CD44 mAb-induced expression of Lex (> 30% increase in Mean Fluorescence Intensity (MFI) by flow cytometry) was accompanied by decreased expression (> 20% decrease in MFI) of its related structure sialyl Lex (sLex). Two non-mutually exclusive processes could account for the increase in Lex expression during myeloid differentiation:neo-synthesis of the Lex epitope and/orde-sialylation of the existing sLex. To test whether increased expression of Lex during CD44-induced differentiation resulted from augmented synthesis, Acute Myeloid Leukemia (AML) cells were treated with anti-CD44 mAb in the presence of 4F-GlcNAc (2-acetamido-1,3,6-tri-O-acetyl-4-fluoro-D-glucopyranose), an inhibitor of poly-N-acetyl-lactosamine synthesis. 4-F-GlcNAc did not significantly alter the increase of Lex induced by the anti-CD44 mAb indicating that the CD44-mediated increase of Lex does not require de-novo polylactosamine synthesis. In presence of the sialidase inhibitor DANA (2,3-dehydro-2-deoxy-N-Acetyl-neuraminic acid) the anti-CD44-induced increase of Lex and decrease of sLex were abrogated indicating that sialidase plays an important role in the modulation of Lex expression during CD44 mAb-induced granulocytic differentiation. Moreover, using the exogenous substrate 4MU-NANA to measure endogenous sialidase activity in AML cells we found that the anti-CD44 mAb Hermes-1 induced a significant increase in the sialidase activity of AML cells, strongly suggesting that CD44-induced differentiation causes the elaboration of endogenous sialidases that are responsible for the modulation of Lex level by converting sLex into Lex. Furthermore, treatment of immature myeloid cells with G-CSF induced a 2-fold increase in sialidase activity, coincident with increased morphological changes of differentiation suggesting that the induction of surface sialidase activity is associated dynamically with the conversion of immature to mature phenotypes among native myeloid cells. Our results unveil a new paradigm, demonstrating a critical role for glycosidase activity in the “biosynthesis” of a key glycan determinant expressed on human cells.

Epigenetic reprogramming of host and viral genes by Human Cytomegalovirus infection in Kasumi-3 myeloid progenitor cells at early times post-infection

2021 ◽  
Author(s):  
Eleonora Forte ◽  
Fatma Ayaloglu Butun ◽  
Christian Marinaccio ◽  
Matthew J. Schipma ◽  
Andrea Piunti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Post Infection ◽  
De Novo ◽  
Critical Role ◽  
Myeloid Cells ◽  
Viral Gene Expression ◽  
Chromatin Accessibility ◽  
Viral Gene ◽  
Dynamic Changes ◽  
Pol Ii

HCMV establishes latency in myeloid cells. Using the Kasumi-3 latency model, we previously showed that lytic gene expression is activated prior to establishment of latency in these cells. The early events in infection may have a critical role in shaping establishment of latency. Here, we have used an integrative multi-omics approach to investigate dynamic changes in host and HCMV gene expression and epigenomes at early times post infection. Our results show dynamic changes in viral gene expression and viral chromatin. Analyses of Pol II, H3K27Ac and H3K27me3 occupancy of the viral genome showed that 1) Pol II occupancy was highest at the MIEP at 4 hours post infection. However, it was observed throughout the genome; 2) At 24 hours, H3K27Ac was localized to the major immediate early promoter/enhancer and to a possible second enhancer in the origin of replication OriLyt; 3) viral chromatin was broadly accessible at 24 hpi. In addition, although HCMV infection activated expression of some host genes, we observed an overall loss of de novo transcription. This was associated with loss of promoter-proximal Pol II and H3K27Ac, but not with changes in chromatin accessibility or a switch in modification of H3K27. Importance. HCMV is an important human pathogen in immunocompromised hosts and developing fetuses. Current anti-viral therapies are limited by toxicity and emergence of resistant strains. Our studies highlight emerging concepts that challenge current paradigms of regulation of HCMV gene expression in myeloid cells. In addition, our studies show that HCMV has a profound effect on de novo transcription and the cellular epigenome. These results may have implications for mechanisms of viral pathogenesis.

scholarly journals Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats

2021 ◽  
Vol 22 (9) ◽  
pp. 4961
Author(s):  
Maria Kovalska ◽  
Eva Baranovicova ◽  
Dagmar Kalenska ◽  
Anna Tomascova ◽  
Marian Adamkov ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Brain Area ◽  
Critical Role ◽  
Cerebrovascular Diseases ◽  
Behavioral Pattern ◽  
Cell Physiology ◽  
Male Wistar Rats ◽  
High Level ◽  
Hippocampal Alterations ◽  
The Impact

L-methionine, an essential amino acid, plays a critical role in cell physiology. High intake and/or dysregulation in methionine (Met) metabolism results in accumulation of its intermediate(s) or breakdown products in plasma, including homocysteine (Hcy). High level of Hcy in plasma, hyperhomocysteinemia (hHcy), is considered to be an independent risk factor for cerebrovascular diseases, stroke and dementias. To evoke a mild hHcy in adult male Wistar rats we used an enriched Met diet at a dose of 2 g/kg of animal weight/day in duration of 4 weeks. The study contributes to the exploration of the impact of Met enriched diet inducing mild hHcy on nervous tissue by detecting the histo-morphological, metabolomic and behavioural alterations. We found an altered plasma metabolomic profile, modified spatial and learning memory acquisition as well as remarkable histo-morphological changes such as a decrease in neurons’ vitality, alterations in the morphology of neurons in the selective vulnerable hippocampal CA 1 area of animals treated with Met enriched diet. Results of these approaches suggest that the mild hHcy alters plasma metabolome and behavioural and histo-morphological patterns in rats, likely due to the potential Met induced changes in “methylation index” of hippocampal brain area, which eventually aggravates the noxious effect of high methionine intake.

Evaluation on the performance fluctuation after water ingestion for a turbofan engine compressor during flight descent

2020 ◽  
pp. 095441002097798
Author(s):  
Lu Yang ◽  
Qun Zheng ◽  
Aqiang Lin
Keyword(s):  
Droplet Diameter ◽  
Pressure Ratio ◽  
Critical Role ◽  
Water Film ◽  
Heavy Rain ◽  
Diameter Distribution ◽  
Turbofan Engine ◽  
Water Ingestion ◽  
The Core ◽  
Engine Compressor

Turbofan engine compressor is most severely threatened by the entry of liquid water during flight descent. This study aims to deeply understand the fluctuations of compressor performance parameters caused by water ingestion through frequency spectrum analysis. The water content and droplet diameter distribution are determined based on the real heavy rain environment. Results reveal that most of the droplets actually entering the core compressor have a particle size of less than 100 μm. In addition, the formation and motion of water film plays a critical role in affecting the fluctuation characteristics. Water ingestion deteriorates the compression performance and aggravates the unsteady fluctuations of the fan. However, the performance of the core compressor is less affected by water ingestion, but their fluctuations are still exacerbated. For some important parameters, such as inlet mass flow rate, total pressure ratio, total temperature ratio, compression work and efficiency, their main frequency of fluctuation are switched from the original blade passing frequency to the rotor passing frequency, and their amplitudes are correspondingly amplified to varying degrees. These phenomena can be observed in both the fluctuations of the fan and core compressor. Moreover, the operating point of them will be in the long-period and large-amplitude fluctuations, which leads them experiences the non-optimal state for a long time and threatens their operating stability.

scholarly journals Regulation of Mineralocorticoid Receptor Expression during Neuronal Differentiation of Murine Embryonic Stem Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2244-2254 ◽  
Author(s):  
Mathilde Munier ◽  
Geri Meduri ◽  
Say Viengchareun ◽  
Philippe Leclerc ◽  
Damien Le Menuet ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Mineralocorticoid Receptor ◽  
Fluorescent Protein ◽  
Morphological Changes ◽  
Critical Role ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Receptor Expression ◽  
Neuronal Markers ◽  
Mature Neurons

Mineralocorticoid receptor (MR) plays a critical role in brain function. However, the regulatory mechanisms controlling neuronal MR expression that constitutes a key element of the hormonal response are currently unknown. Two alternative P1 and P2 promoters drive human MR gene transcription. To examine promoter activities and their regulation during neuronal differentiation and in mature neurons, we generated stably transfected recombinant murine embryonic stem cell (ES) lines, namely P1-GFP and P2-GFP, in which each promoter drove the expression of the reporter gene green fluorescent protein (GFP). An optimized protocol, using embryoid bodies and retinoic acid, permitted us to obtain a reproducible neuronal differentiation as revealed by the decrease in phosphatase alkaline activity, the concomitant appearance of morphological changes (neurites), and the increase in the expression of neuronal markers (nestin, β-tubulin III, and microtubule-associated protein-2) as demonstrated by immunocytochemistry and quantitative PCR. Using these cell-based models, we showed that MR expression increased by 5-fold during neuronal differentiation, MR being preferentially if not exclusively expressed in mature neurons. Although the P2 promoter was always weaker than the P1 promoter during neuronal differentiation, their activities increased by 7- and 5-fold, respectively, and correlated with MR expression. Finally, although progesterone and dexamethasone were ineffective, aldosterone stimulated both P1 and P2 activity and MR expression, an effect that was abrogated by knockdown of MR by small interfering RNA. In conclusion, we provide evidence for a tight transcriptional control of MR expression during neuronal differentiation. Given the neuroprotective and antiapoptotic role proposed for MR, the neuronal differentiation of ES cell lines opens potential therapeutic perspectives in neurological and psychiatric diseases.

scholarly journals A novel transcript encoding an N-terminally truncated AML1/PEBP2 alphaB protein interferes with transactivation and blocks granulocytic differentiation of 32Dcl3 myeloid cells.

1997 ◽  
Vol 17 (7) ◽  
pp. 4133-4145 ◽  
Author(s):  
Y W Zhang ◽  
S C Bae ◽  
G Huang ◽  
Y X Fu ◽  
J Lu ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Protein Product ◽  
Terminal Region ◽  
Human Leukemia ◽  
Granulocytic Differentiation ◽  
Runt Domain ◽  
Rnase Protection ◽  
Novel Transcript

The gene AML1/PEBP2 alphaB encodes the alpha subunit of transcription factor PEBP2/CBF and is essential for the establishment of fetal liver hematopoiesis. Rearrangements of AML1 are frequently associated with several types of human leukemia. Three types of AML1 cDNA isoforms have been described to date; they have been designated AML1a, AML1b, and AML1c. All of these isoforms encode the conserved-Runt domain, which harbors the DNA binding and heterodimerization activities. We have identified a new isoform of the AML1 transcript, termed AML1 deltaN, in which exon 1 is directly connected to exon 4 by alternative splicing. The AML1 deltaN transcript was detected in various hematopoietic cell lines of lymphoid to myeloid cell origin, as revealed by RNase protection and reverse transcriptase PCR analyses. The protein product of AML1 deltaN lacks the N-terminal region of AML1, including half of the Runt domain, and neither binds to DNA nor heterodimerizes with the beta subunit. However, AML1 deltaN was found to interfere with the transactivation activity of PEBP2, and the molecular region responsible for this activity was identified. Stable expression of AML1 deltaN in 32Dcl3 myeloid cells blocked granulocytic differentiation in response to granulocyte colony-stimulating factor. These results suggest that AML1 deltaN acts as a modulator of AML1 function and serves as a useful tool to dissect the functional domains in the C-terminal region of AML1.

Transcriptional regulation of the human CAD gene during myeloid differentiation

1987 ◽  
Vol 7 (5) ◽  
pp. 1961-1966
Author(s):  
G N Rao ◽  
E S Buford ◽  
J N Davidson
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Morphological Changes ◽  
Transcriptional Level ◽  
Carbamoyl Phosphate ◽  
Aspartate Transcarbamylase ◽  
Trans Retinoic Acid ◽  
Beta Actin ◽  
Cad Gene ◽  
Cad Protein

CAD codes for a trifunctional protein involved in the catalysis of the first three enzymatic activities in the de novo pyrimidine biosynthetic pathway, namely, carbamoyl-phosphate synthetase II (EC 6.3.5.5), aspartate transcarbamylase (EC 2.1.3.2), and dihydroorotase (EC 3.5.2.3). CAD regulation was studied in the human promyelocyte leukemic line HL-60 as it differentiated into monocytic or granulocytic lineages after induction by 12-O-tetradecanoylphorbol-13-acetate or trans-retinoic acid and dibutyryl cyclic AMP, respectively. Within 12 h of induction of HL-60 cells with either inducer, total cellular levels of CAD RNA essentially disappeared. On the other hand, no apparent decreases in beta-actin RNA levels were seen even 48 h after HL-60 cells were induced, as compared with untreated cells. With nuclear runoff assays, it was clearly shown that the inactivation of CAD gene expression during the induction of HL-60 cells with either inducer was at the transcriptional level. The nuclear runoff experiments also demonstrated that the CAD gene expression was shut down in less than 4 h after induction, well before morphological changes were observed in these cells. At the enzymatic level, the activity of aspartate transcarbamylase, one of the three enzymes encoded by the CAD gene, decreased by about half within 24 h of induction, suggesting a CAD protein half-life of 24 h in differentiating HL-60 cells. Nevertheless, this means that significant levels of aspartate transcarbamylase activity remained even after the cells have stopped proliferating. From the RNA data, it is clear that CAD gene expression is rapidly turned off as promyelocytes begin to terminally differentiate into macrophages and granulocytes. We suspect that the inactivation of the CAD gene in induced HL-60 cells is a consequence of the differentiating cells leaving the cell cycle and becoming nonproliferating.

Revising the Assumption that Ḥadīṯ Studies Flourished in the 11th/17th-Century Ḥiǧāz: Ibrāhīm al-Kūrānī’s (d. 1101/1690) Contribution

Arabica ◽  
2021 ◽  
Vol 68 (1) ◽  
pp. 1-35
Author(s):  
Naser Dumairieh
Keyword(s):  
General Framework ◽  
18Th Century ◽  
Critical Role ◽  
17Th Century ◽  
Main Interest ◽  
Islamic World ◽  
The Core ◽  
Revival Movement ◽  
Almost All

Abstract The Ḥiǧāz in the 11th/17th century has long been considered the center of a “revival” movement in ḥadīṯ studies. This assumption has spread widely among scholars of the 11th-/17th- and 12th-/18th-century Islamic world based on the fact that the isnāds of many major ḥadīṯ scholars from almost all parts of the Islamic world from the 11th/17th century onward return to a group of scholars in the Ḥiǧāz. The scholarly group that is assumed to have played a critical role in the flourishing of ḥadīṯ studies in the 11th/17th-century Ḥiǧāz is called the al-Ḥaramayn circle or network. However, to date, there have been no studies that investigate what was actually happening in that century concerning ḥadīṯ studies. Examining the actual ḥadīṯ studies of one of the scholars at the core of al-Ḥaramayn circle, i.e. Ibrāhīm b. Ḥasan al-Kūrānī, will unpack the main interest of Ḥiǧāzī scholars in ḥadīṯ literature, reveal previously unstudied aspects of ḥadīṯ studies in the 11th/17th-century Ḥiǧāz, correct some unexamined assumptions, and situate the ḥadīṯ efforts of scholars of the 11th/17th-century Ḥiǧāz within a general framework of developments within ḥadīṯ studies.

scholarly journals PRELUDE Prospective Study of the Serranator Device in the Treatment of Atherosclerotic Lesions in the Superficial Femoral and Popliteal Arteries

2018 ◽  
Vol 26 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Andrew Holden ◽  
Andrew Hill ◽  
Andrew Walker ◽  
Brendan Buckley ◽  
Stephen Merrilees ◽  
...  
Keyword(s):  
De Novo ◽  
Balloon Catheter ◽  
Vessel Diameter ◽  
Primary Patency ◽  
Lesion Length ◽  
Chronic Total Occlusions ◽  
The Core ◽  
Safety Endpoint ◽  
Exciting Potential ◽  
Primary Safety Endpoint

Purpose: To evaluate the safety and efficacy of the Serranator Alto PTA Serration Balloon Catheter in subjects with peripheral artery disease in the superficial femoral and popliteal arteries. Materials and Methods: A prospective, multicenter, single-arm feasibility study enrolled 25 patients (mean age 66 years; 18 men) to evaluate Serranator inflation and postinflation effects under monitoring by independent core laboratories. Inclusion criteria were claudication or ischemic rest pain, de novo lesions or native artery restenosis, >70% stenosis, lesion length <10 cm, and a reference vessel diameter of 4 to 6 mm. Chronic total occlusions (CTO) up to 6 cm in length were allowed (n=8). The primary safety endpoint was 30-day major adverse events. Primary efficacy outcome was device success with final diameter stenosis <50%. The secondary objective was to confirm the presence of serrations across the lesions using optical coherence tomography (OCT) or intravascular ultrasound (IVUS) following treatment in a subset of 10 subjects. Follow-up evaluations were conducted at 30 days and 6 months. Results: Technical success of device delivery and retrieval was 100%. The primary safety endpoint was met, with no patients experiencing a major adverse event in the first 30 days. Pretreatment stenosis of 88% was reduced to 23%. One stent was implanted for grade D dissection in a CTO. The core laboratory–adjudicated primary patency was 100% at 1 month and 64% at 6 months. Serrations were confirmed in all 10 OCT/IVUS images reviewed by the core laboratory. The Rutherford category showed significant and sustained improvement at 6 months. Conclusion: The Serranator is a safe and efficacious angioplasty balloon catheter system. This new design provides an exciting potential for optimizing vessel preparation and aiding drug delivery.

scholarly journals Sodium Tanshinone IIA Sulfonate Prevents Angiotensin II-Induced Differentiation of Human Atrial Fibroblasts into Myofibroblasts

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Tangting Chen ◽  
Miaoling Li ◽  
Xuehui Fan ◽  
Jun Cheng ◽  
Liqun Wang
Keyword(s):  
Angiotensin Ii ◽  
Critical Role ◽  
Water Soluble ◽  
Collagen I ◽  
Tanshinone Iia ◽  
Ang Ii ◽  
Induced Differentiation ◽  
Fibroblast Migration ◽  
Collagen Iii ◽  
Sodium Tanshinone Iia Sulfonate

Differentiation of atrial fibroblasts into myofibroblasts plays a critical role in atrial fibrosis. Sodium tanshinone IIA sulfonate (DS-201), a water-soluble derivative of tanshinone IIA, has been shown to have potent antifibrotic properties. However, the protective effects of DS-201 on angiotensin II- (Ang II-) induced differentiation of atrial fibroblasts into myofibroblasts remain to be elucidated. In this study, human atrial fibroblasts were stimulated with Ang II in the presence or absence of DS-201. Then, α-smooth muscle actin (α-SMA), collagen I, and collagen III expression and reactive oxygen species (ROS) generation were measured. The expression of transforming growth factor-β1 (TGF-β1) and the downstream signaling of TGF-β1, such as phosphorylation of Smad2/3, were also determined. The results demonstrated that DS-201 significantly prevented Ang II-induced human atrial fibroblast migration and decreased Ang II-induced α-SMA, collagen I, and collagen III expression. Furthermore, increased production of ROS and expression of TGF-β1 stimulated by Ang II were also significantly inhibited by DS-201. Consistent with these results, DS-201 significantly inhibited Ang II-evoked Smad2/3 phosphorylation and periostin expression. These results and the experiments involving N-acetyl cysteine (antioxidant) and an anti-TGF-β1 antibody suggest that DS-201 prevent Ang II-induced differentiation of atrial fibroblasts to myofibroblasts, at least in part, through suppressing oxidative stress and inhibiting the activation of TGF-β1 signaling pathway. All of these data indicate the potential utility of DS-201 for the treatment of cardiac fibrosis.

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