We also found that memory B cells from our patients expressed higher levels of CD5 compared to healthy controls. These cells are known to produce low-affinity polyreactive antibodies (natural antibodies), which recognize autoantigens or conserved structures on self-antigens such as polysaccharide residues [21]. They have a reduced capacity to enter the cell cycle and have a longer lifespan. Although the precise role of these cells in autoimmunity is still obscure, the numbers of peripheral CD5+ B cells were found to be increased CDK inhibitor in several autoimmune diseases, such as rheumatoid arthritis, primary Sjögren’s syndrome, autoimmune thyroid disease and multiple sclerosis [22]. Therefore, it seems that these cells

might play a role in the pathogenesis of autoimmune diseases [23]. The finding of low C4 levels, along with low functional C1INH in HAE, remains the most important immunological finding in this disease. C4 is important for the immune complex solubilization and removal [24]. Therefore, inherited deficiencies of C1q and C4 are associated with the chronic activation of the classical complement pathway and the development of autoimmune disease

such as lupus-like disease early in life [25]. Activation of the classical complement arm through immune complexes causes the production of C3 convertase, and the cleavage of C3 by C3 convertase leads to the production of C3b being an essential product for the immune complex removal. In addition, deficiencies of C4 render mice

GS 1101 unable to clear apoptotic cells/debris [26]. Mevorach et al. demonstrated that apoptotic materials are immunogenic and accelerate the production of autoantibody in mice not prone to autoimmunity [27]. Apoptotic material, especially when associated with microbial products in the form of immune complexes (ICs), might activate autoreactive B lymphocytes and induce serum autoantibodies [28]. One can speculate that the persistence of ICs could possibly activate B cell receptors and up-regulate the expression of TLR-9, allowing HAE patients to overproduce autoantibodies. Another possible explanation for the over-activation of B cells in HAE could be through increased signalling of the human complement receptor type 2 (CR2) on B cells. GBA3 CR2 (CD21) plays a pivotal role in the activation and proliferation of B cells and is a prerequisite for T-dependent immune responses. Engagement of CR2 with the B cell receptor lowers the threshold required for B cell activation by an antigen, enhances cell activation, reduces inhibitory signals and prevents apoptosis [29–32]. Only seven of our 61 (11·4%) patients had a defined immunoregulatory disorder. This incidence of immunoregulatory disorders is similar to the 12% found by Brickman et al. and 11·5% that was found by Farkas et al. [11,13]. It is not yet clear if this finding represents increased incidence compared to that in the general population.

[94-96] The repertoire of CD1d-presented self-antigen is responsive to an APC activation state. Staining with tetramerized iNKT TCR, and comparison of the repertoire of CD1d-associated

self-GSL in resting and LPS (TLR4)-stimulated myeloid DC, shows that TLR stimulation of DC causes an increase in presentation of iNKT-activating CD1d ligands.[30, 37] Triggering of TLR4 and TLR7 or TLR9 on DC activates iNKT cells, and this activation requires APC synthesis of charged β-linked GSL.[29] In inflammation, Selleckchem PLX4032 APC levels of lysophosphatidylcholine increase, though lysophosphatidylcholine is only a weak activator of iNKT cells.[41] A more important role is indicated for β-GlcCer. It is synthesized in response to TLR agonists, and inhibition of this synthesis impairs iNKT responses to DC cultured with bacteria. Further, bacterial infection of mice leads to accumulation of β-GlcCer at sites of E. coli or Streptococcus pneumoniae infection.[11]

In mice, TLR stimulation PXD101 order of DC inhibits α-galactosidase A, which normally degrades lysosomal self-antigens to prevent full iNKT activation, though this mechanism is unlikely to be important in humans.[97, 98] CD1d and DC-dependent but TLR-independent activation of iNKT cells has been reported in responses to fungi including Aspergillus and Candida.[99] Fungal cell wall β-1,3-glucans bind pattern recognition receptors on APC to stimulate IL-12 release, which activates Tideglusib autoreactive iNKT cells. Invariant NKT cells also form part of the response to helminths, though the mechanism remains partly delineated. There is a requirement for CD1d, and for schistosome egg recognition by DC, though neither IL-12 nor TLR signalling is necessary.[100] Activation of iNKT cells in mouse cytomegalovirus infection is antigen-independent, relying on APC-derived IL-12.[101-103] In this context, iNKT cells behave as innate lymphocytes, amplifying the

immune response, a capacity that widens the range of pathogen defences in which they could be involved. The APC-derived cytokines have also been demonstrated to drive antigen-independent iNKT activation in a model of E. coli infection.[104] Priming of iNKT cells to be more responsive to IL-12 in the absence of foreign antigen 85 suggests that there is a hierarchy of activation stimuli for iNKT cells. For example, in response to Salmonella typhimurium, IL-12 amplifies a weak response to self-antigen,[24, 5] and DC from patients with advanced cancer are better able to activate iNKT cells if supplemented with IL-12.[105] If exogenous antigen, self-antigen and IL-12 are all present, which is the most important in activating iNKT cells? Many studies exploring iNKT-cell activation use hybridoma cell lines, which may lack the ability to respond to both antigen and cytokine signals. To address this, Brigl et al.

A. C. has received personal compensation Alectinib cost for activities with Almirall Hermal GmbH, Bayer Schering, Biogen Idec, Merck Serono, Novartis and Teva Neuroscience, research support from Bayer Schering, Biogen Idec, Merck Serono and Novartis and research grants from the German Ministry for Education and Research [BMBF, ‘German Competence Network Multiple Sclerosis’

(KKNMS), CONTROL MS, 01GI0914]. “
“Analysis of the molecular mechanisms governing the ability of IL-10 to keep inflammation under control has highlighted the existence of a great degree of plasticity and specificity with regard to innate immune cells. In this respect, neutrophils represent a perfect example of innate immune cells conditioned by external signals (for instance, by LPS), as well as by intracellular regulatory pathways, that render them optimally responsive to IL-10 only

when required. The focus of this review are the recent experimental findings that have uncovered the sophisticated and complex molecular mechanisms responsible for the modulation of pro- and anti-inflammatory cytokine production Birinapant by IL-10 in neutrophils and other innate immune cells. Understanding how IL-10 exerts its anti-inflammatory response, particularly in the case of neutrophils, will provide novel clues leading, hopefully, to Bay 11-7085 the therapeutic control of neutrophil-driven inflammatory reactions, such as septic infections, rheumatoid arthritis, osteoarthritis and chronic obstructive pulmonary disease. The biological activities of IL-10 function, in part, as key homeostatic mechanisms that control the degree and duration of the inflammatory response. IL-10, in fact, acts as a potent anti-inflammatory cytokine by conditioning the activation and function of innate and Ag-specific immune cells. Accordingly, a crucial effect of IL-10 is its ability to

selectively block the expression of pro-inflammatory genes encoding cytokines and chemokines in myeloid cells activated by PRR ligands, such as LPS, lipoteichoic acid or the TLR9 agonist, CpG, thereby dampening inflammation 1. By contrast, IL-10 simultaneously enhances the expression and production of anti-inflammatory molecules 1. The molecular mechanisms whereby IL-10 modulates the production of pro- and anti-inflammatory cytokines by target cells are, however, incompletely understood. Nonetheless, a general consensus exists regarding the following IL-10-triggered signaling steps, occurring both in murine and in human systems.

“
“Why infants prefer to look at and use information provided by some informants over others was examined in four experiments. In each experiment, 52 12-month-old infants participated. In Experiment 1, a familiar expert and a familiar nonexpert and in Experiment 2, a novel expert and a novel nonexpert presented an ambiguous object and provided positive information. see more In both experiments, the infants preferred to look at the expert and regulated their behavior more in accordance with positive information provided by the expert, regardless of she was novel or

more familiar. In Experiment 3, a familiar expert and a familiar nonexpert and in Experiment 4, a novel expert and a novel nonexpert presented an ambiguous object and provided negative information. In both experiments, the infants looked more at the expert and regulated their behavior more in accordance with negative information provided by the expert,

regardless of she was novel or more familiar. The results support an expertise perspective of infant behavior in social-referencing situations. “
“This study examined how look dynamics contribute to infants’ emerging novelty preferences. Time-series analyses were used to study the temporal nature of looking displayed by 3- to 5-month-old infants during a serial paired-comparison task. Evidence was found only for short-term stability: Novelty preferences and side biases were not stable from one visit anti-PD-1 monoclonal antibody to the next, but looking was consistent from one moment to the next producing stability within trials and temporarily across trials leading to the formation of behavioral runs. Persistence in looking left or right across multiple trials did not change from one visit to the next, but persistence in looking at familiar stimuli declined with age. By Visit 3, familiarity runs occurred less often than did novelty runs. Frequent but highly variable runs, including surprisingly late familiarity preferences, suggest that overall side biases and novelty preferences found during visual

preference tasks are emergent phenomena affected by moment-to-moment changes in looking. “
“While the specificity of infants’ early lexical representations has been studied extensively, Org 27569 researchers have only recently begun to investigate how words are organized in the developing lexicon and what mental representations are activated during processing of a word. Integrating these two lines of research, the current study asks how specific the phonological match between a perceived word and its stored form has to be in order to lead to (cascaded) lexical activation of related words during infant lexical processing. We presented German 24-month-olds with a cross-modal semantic priming task where the prime word was either correctly or incorrectly pronounced.

The majority of patients presented with mild myopathy and prominent cardiomyopathy. Fifteen of 16 deceased cases died of cardiac causes. Of the 25 patients alive, 24 patients developed cardiac abnormalities with disease progression. Muscle specimens from nine patients were investigated in various morphological examinations. Gene sequencing and cell transfections were performed to determine whether the mutant desmin formed intermediate filaments. Paclitaxel Results: Muscle biopsies revealed 5 cases with dystrophy-like patterns and amorphous material

deposits; four other cases showed myopathy-like patterns with cytoplasmic bodies or nemaline bodies. Desmin and multiple proteins aggregated in the affected fibres. Six novel mutations Raf inhibitor and one previously reported mutation in the desmin gene were identified in the patients. All the mutant desmin genes except E457V produced multiple desmin-positive clumps or abnormal solid large aggregates in transfected cells. Conclusions: This study enlarges the spectrum of desmin mutations and geographic distribution of desminopathy. Although many novel mutations were identified in Chinese patients, the main clinical and myopathological findings were similar to those in Caucasian patients.

Cardiac conduction abnormalities were prominent and usually appeared later than skeletal myopathy. The myopathology exhibited some heterogeneity among our patients, but the pathological changes were not indicative of the mutation location in the desmin gene. Desmin is a primary element of the intermediate filament network in skeletal, cardiac and smooth muscle cells. Desmin plays a critical role in connecting myofibrils to each other and to the sarcolemma, mitochondria and nuclei from the periphery Idoxuridine of the Z line structures [1]. Desmin protein consists of a highly conserved central α-helical rod domain flanked by globular N-terminal head and C-terminal tail domains. The α-helical rod domain of desmin includes four helixes: 1A, 1B, 2A and 2B [2]. Mutations of the

desmin gene, especially in the helix 2B and 1B of the rod domain, are associated with desminopathy [3–5]. Desminopathy is a major subgroup of myofibrillar myopathy, clinically characterized as cardiac and skeletal myopathy [6,7]. Most cases exhibit an autosomal dominant inherited pattern, but autosomal recessive and de novo mutations are also observed [8,9]. Patients usually become symptomatic in the second to the third decade of life. The most typical symptoms manifest as slowly progressive weakness of distal muscles in the lower limbs, later spreading to the upper limbs, neck, trunk and bulbar muscles [3,10]. However, cardiac symptoms may be dominant in some patients [11–13], and are the leading cause of death in most patients [6,14].

At the age of 33 years, the patient suffered a pathological fracture in the right femoral neck and could no longer walk. As for psychological symptoms, the patient was apathetic and exhibited behavioral Ibrutinib molecular weight abnormalities. At the age of 34 years, the patient had an epileptiform seizure, and although the seizures gradually subsided,

voluntary upper limb movements and speech became difficult. In response to external stimulation, the patient could move his eyeballs and swallow a liquid substance placed in the mouth. At the age of 38 years, he could not move or speak and subsequently died. Systemic emaciation and subcutaneous fat tissue degeneration were marked, the liver, spleen, and lymph nodes were severely atrophied, and abnormal lipid deposition was not seen at all. In long bones, such as the femur, tibia, fibula, and ribs, the medullary cavity at both ends was filled with yellow opaque gelatinous substances,

matching the translucent cystic lesions seen on X-rays, the bone substance was highly resorbed, and the bone cortex was so thin that it could be damaged when pressed by a finger. In the substances, numerous membranocystic changes were widely distributed on light microscopy, and surrounding fat cells and other cell components were markedly reduced (Fig. 1). NVP-BKM120 in vivo Membranocystic lesions were also seen in the bone fatty marrow, subepicardium, mediastinum, mesentery, thymus, systemic adipose tissue around the kidney and lymph nodes, adrenal glands, testes, hepatic sinusoids, and pulmonary vascular lumina. Membranous structures were positive for Sudan III, stained blue Org 27569 with Nile blue, and most were positively stained by Luxol fast blue. The brain weighed 1050 g. As for macroscopic findings, symmetric systemic atrophy of the brain, in particular severe atrophy of the occipital and temporal white matters, was seen. The gyrus was narrow, the cerebral sulcus was somewhat broad and deep, and the meninx was smooth. On cross-sections, marked white matter atrophy was confirmed. The boundary between the white and gray matters was slightly unclear. The basal ganglia were mildly atrophied,

and the ventricles were severely enlarged in a symmetrical manner. Bleeding or softening was not confirmed. No notable findings were seen in the cerebellum, pons or medulla oblongata. The spinal cord was not examined. As for histological findings, the white matter was broadly degenerated, and diffuse sclerosis accompanied by astroglial proliferation was confirmed (Fig. 2). Gemistocytic astrocyte was the major component, and fibrillary gliosis was mild. Inflammatory cellular infiltration was absent. Myelin sheath staining confirmed severe demyelination, but U-fibers were relatively conserved. Axonal degeneration and destruction were marked, and the axons were bloated in a balloon fashion and ruptured (Fig. 3), and positively stained using Sudan III or PAS.

First, we evaluated the qualities of the BMT model. Multilineage-full

chimerism in the case of BMT using fully allogeneic BMC and multilineage-mixed chimerism in the case of BMT using mixed BMC were confirmed in the PBL of all recipients prior to tumour inoculation (Fig. 4A and data not shown). As previously reported, a small population of recipient-derived radio-resistant T cells were detected in recipients transplanted with BL6 BMC (the lower right dot plot in Fig. 4A). However, these T cells showed no alloresponses [29] and so should not affect the survival time of injected allogeneic DC. The B-cell and myeloid lineage chimerism find more in the PBL was complete in the recipients transplanted with BL6 BMC (the upper right dot plot in Fig. 4A and data not shown). This suggests that the bone marrow haematopoietic cells had been completely replaced by donor-derived BMC. We also assessed the chimerism of the DC in the lymph nodes (inguinal and axillary) and tumours of the B/c recipients. A significant CP-868596 cost percentage of recipient-derived DC was detected in the lymph nodes of recipients transplanted with BL6 BMC (Fig. 4B). More than 60% of residual B/c recipient-derived H-2Kd positive DC in the cutaneous draining lymph nodes expressed DEC205 and I-Ad high, both markers

found on Langerhans cells (data not shown) [34]. This suggests that these cells were derived from Langerhans cells repopulated from the radio-resistant progenitor cells in the cutaneous niche [35]. Because Langerhans progenitor cells in the cutaneous niche are destroyed by any contaminating donor-derived T cells

that mediate graft-versus-host disease (GVHD) [35], the presence of host-derived Langerhans cells in the draining lymph nodes in this study suggests that the T-cell depletion of the donor BMC was complete. This is supported by the fact that we observed no GVHD response in these mice; this observation was confirmed by histological analysis at autopsy (data not shown). To the contrary, almost all tumour-associated DC were positive for H-2Kb and negative for H-2Kd (Fig. 4B). This suggests that the tumour-associated DC were derived from donor BMC. Taken together, we judged that the developed BMT model was qualitatively appropriate to evaluate the three factors individually in ITADT. Surprisingly, we found that ITADT Pomalidomide price using BL6 DC showed a significant antitumour effect in terms of tumour growth suppression as well as ITADT using B/c DC in recipients of mixed BMC (BL6+ B/c B/c), despite the MHC incompatibility of the injected BL6 DC (Fig. 4, middle graph). However, ITADT using BL6 DC did not show any significant antitumour effect in recipients of BL6 BMC, despite the fact that these recipients were tolerant to BL6 (Fig. 4, left-hand graph), while ITADT using B/c DC did show a significant antitumour effect in recipients of BL6 BMC. In recipients of syngeneic BMC (B/c B/c), ITADT using B/c DC showed a significant antitumour effect.

The subjects were randomly assigned to either the control arm (supportive therapy alone) or the itraconazole arm (itraconazole 400 mg day−1 with supportive click here therapy). The randomisation sequence was computer generated using the statistical package StatsDirect for MS-Windows (Version 2.7.2, England, StatsDirect Ltd, 2005. http://www.statsdirect.com). The assignments were placed in sealed opaque envelopes and each patient’s assignment to a particular group was made sequentially. Blinding of treatment allocation was not possible. Itraconazole (Fungitrace, Lifecare Pharma, Gurgaon, India) was administered at a dose

of 200 mg twice a day along with meals (or orange juice) for 6 months. Drug levels of itraconazole were not performed. During the study period, no proton pump inhibitors or other acid reducing medicines were allowed. Adherence to itraconazole was assessed by instructing patient to bring the empty pill covers of the drug. Supportive therapy included antitussives (combination of dextromethorphan 10 mg, triprolidine 1.25 mg and phenylephrine 5 mg twice daily), iron and vitamin supplements (100 mg https://www.selleckchem.com/products/LBH-589.html of elemental iron as ferrous ascorbate; folic acid 1 mg day−1), and bronchial artery embolisation and/or surgery as and when indicated. All patients underwent the following investigations

at baseline: chest radiograph, CT of the chest, serum precipitins against Aspergillus species, flexible bronchoscopy, sputum/BALF culture for Aspergillus and mycobacteria, spirometry, complete blood count, liver function tests and electrocardiogram. Aspergillus skin test and total serum IgE levels were performed to exclude ABPA. At 6 months CT chest, spirometry and complete blood count were repeated. Liver function tests were performed every 1–2 months or immediately if patients complained of jaundice, easy fatiguability, loss of appetite or right upper quadrant abdominal pain. All data were recorded on a

standard questionnaire. Clinical response was classified as improved, stable or worsened based on assessment of patient’s sense of well-being, gain in weight, improvement in cough and exercise capacity, decrease in the number, and frequency Nintedanib (BIBF 1120) and quantity of haemoptysis. Radiological response was considered present if there was decrease in the size/number of the fungal balls, attenuation of the paracavitary infiltrates or pleural fibrosis. The response was assessed objectively by measuring the longest diameter of various lesions and a 50% reduction was taken as criteria for improvement. Overall response was classified as[2]: (a) improved: improved or stable clinical response and radiologically improved or stable disease; and (b) failed: worsening of symptoms or radiological progression. All outcomes were assessed at the end of 6 months of therapy. Patients were followed up for at least 6 months following completion of treatment.

Following stimulation in a 96-well

flat bottom plate, purified B cells were incubated with 4 μM DHE (Molecular Probes) as previously described by Laniewski and Grayson [45]. Surface staining was performed by incubating the cells in a 1:100 dilution of rat anti-mouse B220-allophycocyanin (BD Pharmingen) in 2% FACS Buffer (phosphate buffered saline plus 2% FCS) for 30 min on ice. Cells were washed three times and fixed in 2% paraformaldehyde (Sigma-Aldrich). Purified (1.5 × 106) HIF inhibitor review B cells were seeded into wells containing an air-dried, poly-L-lysine (0.01% solution, Sigma-Aldrich)-coated coverslip for 30 min at room temperature. After washing with PBS, cells were stimulated in the presence or absence of 10 μg/mL anti-IgM or 0.2

mM hydrogen peroxide at 37°C. Additionally, one sample was pretreated with 20 mM NAC for 1 h prior to stimulation. At the end of each timepoint, samples were washed, incubated in vehicle or dimedone, and processed for confocal microscopy according to Seo and Carroll [25] using a 1:500 dilution of anti-dimedone antibody (Millipore) and a secondary goat anti-rabbit Alexa-Fluor 488 (Invitrogen). Following sulfenic acid staining, cells were stained with DRAQ5 (Cell Signaling) and mounted with selleck screening library ProLong Gold anti-fade reagent (Invitrogen) according to manufacturer’s protocol. 12-Bit images were acquired using a Zeiss LSM 510 confocal laser scanning microscope with a 63× magnification objective lens. For each experiment, exposure settings were determined to avoid saturation and were used for all samples in order to compare intensities. Methocarbamol The open source software ImageJ (National Institutes of Health) was used to quantify cysteine sulfenic acid levels within the nucleus and cytoplasm. The mean fluorescent intensity within the borders of the cell and nucleus was determined. To determine the cytoplasmic fluorescence, the nuclear value was subtracted from the whole cell value. Six fields of view were analyzed for each condition. Purified (2 × 106) B cells were stimulated with 10 μg/mL anti-IgM, washed one time with PBS, and lysed in the presence

of 50 mM Tris-HCl, 100 mM NaCl, 20 mM β-glycerophosphate, 0.1% SDS, 0.5% sodium deoxycholate, 0.5% Igepal, 0.5% Triton X-100, 1 mM Na3VO4, 20 mM NaF, 1 mM PMSF, 10 μg/mL aprotinin, 10 μg/mL leupeptin, and 1 mM dimedone. After incubating on ice for 30 min, samples were stored at −80°C. For biotin-based affinity capture experiments, purified B cells (4 × 106) were stimulated with 10 μg/mL anti-IgM, washed one time with PBS, and lysed in the presence of 50 mM Tris-HCl, 100 mM NaCl, 100 μM DTPA, 20 mM β-glycerophosphate, 0.1% SDS, 0.5% sodium deoxycholate, 0.5% Igepal, 0.5% Triton X-100, 1 mM Na3VO4, 20 mM NaF, 1 mM PMSF, 10 μg/mL aprotinin, 10 μg/mL leupeptin, 200 units of catalase, 10 mM N-ethyl-maleimide, and 5 mM DCP-Bio1 [46].

The expression levels of NKG2D and 2B4 (CD244)

are similar for dNK and pNK cells. Like CD56bright CD16neg pNK cells, dNK cells express high levels of CD94/NKG2A inhibitory receptor (see Fig. 2). One striking difference concerns the granularity level. Even if they are poorly cytotoxic, dNK cells express much larger amounts of granzyme A, granzyme B and perforin enriched cytotoxic granules than CD56dim cytotoxic pNK cells.[18, 35, 51, 54] Fine analyses of the dNK cell gene expression profile further highlighted these unique features of dNK cells with distinct properties, such as the expression of NKG2E, Ly-49L and KIR receptors, adhesion molecules, galectin-1 or some members of the tetraspan family Adriamycin solubility dmso (CD9, CD151, CD53, CD63).[17] The precise functions of dNK cells in

Ivacaftor mw vivo are not yet completely understood. Nonetheless, evidence exists for their pivotal contribution to the regulation of tissue homeostasis, a critical process for healthy pregnancy and optimal fetal development. At the same time, their endowment with huge plasticity and their susceptibility to external environmental stimuli should be taken into account for the success of pregnancy. Natural killer cells are named after their spontaneous and natural ability to kill tumours and virus-infected cells without previous sensitization. They belong to the group I of innate lymphoid cells because they produce large amounts of type I cytokines but not type II cytokines. They also secrete a large array of chemokines and other growth factors. In the periphery, CD56dim CD16pos pNK cells are highly cytotoxic, whereas CD56bright CD16neg NK cells are cytokine

producers. In the decidua, dNK cells are devoid of cytolytic activity. The lack of cell cytotoxicity has been linked to default in the polarization of the microtubule organizing centre to the immunological synapse or to failure of the 2B4 receptor to convey activating signals.[54, 55] However, induction of dNK cell cytotoxic function by cytokines, such as IL-15 and IL-18, or ligation of specific activating receptor suggests that the lytic machinery is Carteolol HCl tightly regulated in normal pregnancy but can be triggered by the appropriate stress signal.[49, 55, 56] Our work and other’s clearly suggest that cross-talk at the fetal–maternal interface upholds the cytotoxic function under strict control during healthy pregnancy. Inhibitory pathways involving the binding of the CD94/NKG2A inhibitory receptor to its natural ligand HLA-E expressed by the invasive fetal trophoblasts or the secretion of soluble factors such as HLA-G further comfort the tight regulation of dNK cell function during normal pregnancy.[49, 51, 57] The presence of dNK cells in the vicinity of invasive fetal trophoblasts[58] and spiral arteries is suggestive of their active contribution to trophoblast attraction, which is necessary to promote decidualization and placental development.