It appeared clearly from these models that the abnormal metabolic control, as assessed by hyperglycaemia and glycosuria, the hallmarks of T1D clinical diagnosis, was preceded by a long phase defined as ‘prediabetes’ during which the β cell autoantigen-specific inflammatory response developed silently, yet progressively. Thus, in NOD mice

progressive infiltration of the islets of Langerhans by mononuclear cells, also termed insulitis, evolves in two distinct phases [1]. Insulitis appears by 3–4 weeks of age and up to 8–10 weeks is confined to the periphery of the islets (peri-insulitis) without any sign of active destruction of insulin-secreting β cells. As disease progresses, by 10–14 Rapamycin ic50 weeks of age the infiltrating cells invade the islets quite abruptly, i.e. aggressive insulitis, and

rapid β cell destruction occurs causing overt hyperglycaemia. The orchestrated mechanisms leading to β cell destruction all represent potential targets for therapeutic intervention. These mechanisms involve a central triad constituted by β cells, autoantigen-presenting cells and T lymphocytes. Autoantigen-presenting cells are heterogeneous and include dendritic cells (DCs), LY2606368 concentration macrophages and B lymphocytes. The observation that B cell-deficient NOD mice are disease free indicates that disease development is B cell-dependent [2]. In addition to their antigen-presenting role, macrophages and DCs are also key inflammatory effector cells. T lymphocytes involved in T1D are functionally heterogeneous, comprising pathogenic T cells and specialized subsets of regulatory T cells. β cell destruction involves

pathogenic T cells, as demonstrated by the capacity of ‘diabetogenic’ CD4+ and CD8+ lymphocytes from the spleen of diabetic NOD mice to transfer disease into syngeneic immune-compromised recipients [NOD neonates, irradiated adult NOD mice, NOD severe combined immunodeficiency (SCID) mice][3]. In parallel, there is evidence to show that Elongation factor 2 kinase disease progression is controlled by T cell-mediated immune regulatory circuits involving distinct subsets of regulatory T cells [4,5]. It is also important to stress that β cells must not be viewed simply as ‘passive’ targets that are killed immediately by the immune-mediated insult. In a first step they ‘suffer’ from the inflammatory environment created by the insulitis that, in a partially reversible fashion, inhibits their capacity to secrete insulin but also provides all the premises for establishing ‘cross-talk’ between the β cell and the immune cells and cytokines from the environment [6]. It is only in a second step that the β cell is eventually destroyed through apoptosis. During recent years the epidemiology of T1D has become alarming.

W. Berman (2013) Neuropathology and Applied Neurobiology39, 270–283 Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood–brain barrier disruption: implications for the pathogenesis of multiple sclerosis Aim: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by demyelination of white matter, loss of myelin forming oligodendrocytes, changes in the blood–brain barrier (BBB) and leucocyte infiltration. Myelin

basic protein (MBP) is a component of the myelin sheath. Degradation of myelin is believed www.selleckchem.com/products/AZD0530.html to be an important step that leads to MS pathology. Transmigration of leucocytes across the vasculature, and a compromised BBB participate in the neuroinflammation selleck kinase inhibitor of MS. We examined the expression and regulation of the chemokine (C–C motif) ligand 2 (CCL2) and the cytokine interleukin-6 (IL-6) in human endothelial cells (EC), a component of the BBB, after treatment with MBP. Methods: EC were treated with full-length MBP. CCL2 and IL-6 protein were determined by ELISA. Western blot analysis was used to determine signalling pathways. A BBB model was treated with MBP and permeability was assayed using albumin conjugated to Evan’s blue dye. The levels of

the tight junction proteins occludin and claudin-1, and matrix metalloprotease (MMP)-2 were assayed by Western blot. Results: MBP significantly induced CCL2 and IL-6 protein from EC. This induction was partially mediated by the p38 MAPK pathway as there was phosphorylation after MBP treatment. MBP treatment of a BBB model caused an increase in permeability that correlated with a decrease in occludin and claudin-1, and an induction of MMP2. Conclusion: These data demonstrate that MBP induces chemotactic and inflammatory mediators. MBP also alters BBB permeability and tight junction

PD-1 antibody inhibitor expression, indicating additional factors that may contribute to the BBB breakdown characteristic of MS. “
“Neuroenteric cysts are benign intradural endoderm cysts lined by gastrointestinal (GI) or tracheobronchial epithelial cells. Their malignant transformation is extremely rare and only six cases have been reported. In these cases, tissue lineage of the cystic endoderm cells giving rise to carcinoma was not clearly identified either as respiratory or as GI type. Herein, we report a case of mucinous adenocarcinoma arising from the neuroenteric cyst with broncho-pulmonary differentiation in the right cerebral hemisphere of a Japanese woman in her late 50s. The cyst wall was entirely lined by the following respiratory epithelial components: stratified bronchial ciliated columnar epithelium with basal cells positive for CK5 and p63, terminal bronchiolar Clara cells positive for thyroid transcription factor (TTF)-1, surfactant B and negative for surfactant C, type I pneumocytes positive for TTF-1, negative for surfactant B and C, and type II pneumocytes positive for TTF-1 and surfactant B and C.

Very thorough screening EPZ-6438 nmr of multiple slides revealed only two microscopic foci of early demyelination present in the midbrain and in the deep white matter of the frontal lobe. The meninges showed mild lymphocytic infiltrates slightly more prominent at the base of the brain. The present case is remarkable for the association of PML with RA, intense inflammation in the progressing lesions in the brainstem, and selective involvement of subtentorial compartments. There have only been a few case reports of PML in patients with RA. Amend et al.[22] did not find a single case of RA with PML in studies of 138 469 patients with autoimmune disease. However, in a review of 57 HIV-negative

PML patients from the Mayo Clinic, Aksamit reported approximately 5% with RA, without details about the topography of lesions, pathology or specific treatment.[23] Until 2008, only seven patients with PML associated click here with RA were described, all with typical clinical and pathological presentations.[8-14] Subsequently, eight additional PML cases were found in the group of RA patients treated with humanized monoclonal antibodies, including five

patients taking methotrexate.[15-19] All the RA patients developed typical cerebral lesions and only two (treated with rituximab), displayed inflammatory changes with the presence of T- and B-cells.[15, 18] Classical PML lesions in immunocompromised patients show minimal or no inflammation.[1-3] However, intense inflammation develops in PML cases with immune reconstitution inflammatory syndrome (IRIS), following initiation of highly active antiretroviral treatment in the setting of HIV/AIDS, as well as in HIV-negative patients treated with monoclonal antibodies.[24-26] Clinically, focal inflammation has been reported in about 15% of PML cases using gadolinium-enhanced MRI.[2, 27] Although PML is often defined as a non-inflammatory demyelinating disease, some studies suggest that the frequency of inflammation in non-AIDS patients nearly is probably underestimated,[28] and it appears to be more common in the individuals with minimal immunosuppression or without immunodeficiency. Several

reports indicate that inflammatory PML is associated with better prognosis.[14, 28-31] In the inflammatory form of PML, virus-specific CD8+ T-cells concentrate in largest numbers at the borders of progressing demyelination, known to harbor the greatest load of the virus.[30] Furthermore, CD8+ T-cells can be localized in direct contact with the inclusion-bearing oligodendroglia.[30] Although the inflammatory cells were concentrated at the progressive edge of the glial infection, direct contact of T-cells and oligodendroglia could not be demonstrated in this patient. This phenomenon could be explained by immune response mounted against the viral antigen released from disintegrated oligodendroglial cells, rather than against intact virus-bearing oligodendroglia.

Although iNKT cells are <1% of circulating human T cells, they comprise a potent bridge between

innate and adaptive immunity with capacity to elicit both Th1 and Th2 responses. Further study is HSP tumor needed to improve our understanding of the mechanisms of these effects. Specific therapeutic strategies involving iNKT cells are as yet ill-defined, with results in animal models often being conflicting (e.g. GVHD in mice) [35, 36]. Limited human trials, mostly involving cancer patients, have largely yielded negative results [37–42]. There may be differences in outcomes based on strategies of α-GalCer or other lipid treatments [43–45]. Consideration of dietary and medical interventions to affect lipid metabolism and iNKT cell stimulation may be an interesting and promising strategy. In conclusion, our results show that stimulatory lipids accumulate in the liver soon after sensitization and facilitate the rapid activation of iNKT cells in a CD1d-dependent manner. The exact nature of these lipids, the mechanism of accumulation of stimulatory lipids and complete profile of iNKT cell roles in

CS remain to be determined. The authors declare that they have no competing financial interests. We are indebted to Mrs Madeleine Michaud for her secretarial and administrative skills and to Kathy Harry for assistance in isolating hepatocytes. The authors declare that they have no competing financial interests. Supported by NIH grants AI-59801, AI-07174 and AI-0763669 PI3K inhibitor to PWA; Polish Committee of Scientific Research grant N N401355333 to MS; and Polish Committee of Scientific Research grants N N401000936 and K/ZBW/000172 to MM-S. “
“Programmed death-1 receptor (PD-1) is expressed on T cells following

TCR activation. Binding of this receptor Quinapyramine to its cognate ligands, programmed death ligand (PDL)-1 and PDL-2, down-regulates signals by the TCR, promoting T-cell anergy and apoptosis, thus leading to immune suppression. Here, we find that using an anti-PD-1 antibody (CT-011) with Treg-cell depletion by low-dose cyclophosphamide (CPM), combined with a tumor vaccine, induces synergistic antigen-specific immune responses and reveals novel activities of each agent in this combination. This strategy led to complete regression of established tumors in a significant percentage of treated animals, with survival prolongation. We show for the first time that combining CT-011 and CPM significantly increases the number of vaccine-induced tumor-infiltrating CD8+ T cells, with simultaneous decrease in infiltrating Treg cells. Interestingly, we find that CT-011 prolongs Treg-cell inhibition induced by CPM, leading to a sustainable significant synergistic decrease of splenic and tumor-infiltrated Treg cells. Surprisingly, we find that the anti-tumor effect elicited by the combination of CT-011 and CPM is dependent on both CD8+ and CD4+ T-cell responses, although the antigen we used is a class I MHC-restricted peptide.

Rho- kinase (ROK)-myosin light chain phosphatase (MLCP) pathway and protein kinase C potentiated inhibitor (CPI-17)-MLCP pathway have been proposed as two major pathways for the regulation of smooth muscle contraction.20,21 ROK is a serine/threonine kinase that was believed to play an important role in a variety of cellular functions. Caldesmon (CaD) is one of the proteins that regulate the actin cytoskeleton. There are two CaD dominant isoforms: l-CaD and h-CaD (low and high molecular sizes, respectively).21 In the bladder I/R animal LGK-974 chemical structure study,22 ROK increased at 2-h reperfusion, decreased

significantly following 1-week reperfusion, and returned to control by 2-week reperfusion. MLCK expression significantly decreased as early as ischemia alone and did not recover after reperfusion.

Short-term reperfusion induced ROK overexpression in the bladder muscle layer, indicating a compensatory effect of the bladder in response to the ischemic damage. This suggested that ROK in bladder muscle may be upregulated as a compensatory mechanism to increase Ca2+ sensitization. Decreased ROK levels following 1 week of reperfusion indicated free radical damage to the bladder wall and loss of the compensatory find more ability to sustain bladder contractility. For CaD expressions in the muscle layer, both CaD isoforms had different expressions. h-CaD decreased at ischemia alone and 2-h reperfusion, but significantly increased at 2-week reperfusion; whereas l-CaD significantly decreased at 2-week reperfusion. Decreased h-CaD isoform during early ischemia may be associated with remodeling the cytoskeletal structure and interfering with the generation and maintenance of the additional forces required for ischemia-induced bladder dysfunction. Lin et al. proved the development of I/R injury following bladder outlet obstruction. In

a rabbit obstruction model they found that the content of malondialdehyde, a product of lipid peroxidation induced by I/R, of the detrusor was increased after BOO with persistently increased activity of superoxide dismutase Obatoclax Mesylate (GX15-070) of detrusor mitochondria. The content of high-energy phosphates and the contractility of the detrusor were also decreased. These findings indicate that BOO increases generation of reactive oxygen species (ROS) and enhances lipid peroxidation of detrusor mitochondria. The resulting mitochondrial damages lead to persistently decreased energy production and impaired detrusor function.23 As I/R is the main etiologic factor in several bladder dysfunctions, reducing the level of I/R damage would significantly diminish the progression of bladder dysfunction. Recently, several studies have focused on natural compounds for protecting against I/R-induced bladder dysfunction, such as Antrodia camphorate (AC), coenzyme Q10 (CoQ10), and alpha-lipoic acid (α-LA).

For example, it has been shown that sepsis is sometimes associated with neutropenia,[36] accompanied by peripheral blood and BM myeloid progenitor cell mobilization and differentiation.[37] In the case of eosinophils, there Selleckchem ATM/ATR inhibitor is a documented case of cryptococcal infection combined with sepsis, resulting in eosinophilia in a healthy individual.[38] Likewise, LPS has been shown to influence haematopoietic

dynamics through direct effects on progenitor cells, including rapid myeloid differentiation.[13] Increased Eo/B CFU production after LPS stimulation of CB CD34+ cells may represent a mechanism through which haematopoietic progenitor cells[15, 37] or their resulting mature progeny[39] can help to respond to invading bacterial species during acute infections. These mechanisms may also be operative in allergic (eosinophilic/basophilic) inflammation. Our data are interesting in the context Aloxistatin research buy of the type of immune response that can be generated in response to bacterial agents. Of note, IL-5 is an eosinophil-specific inducing cytokine,[40] whereas GM-CSF-responsive progenitors represent earlier stages of lineage commitment and therefore contribute to the development of several myeloid cells[37] including Eo/B cells, macrophages and

neutrophils. Therefore, the apparent skewing of the Eo/B progenitor population towards GM-CSF-responsive (Fig 1a), as opposed to IL-5-responsive, lineages (Fig 1b), with noted increases in GM CFU (data not shown), suggests that the progenitor response to LPS involves production of multi-cellular Astemizole (Eo/B[39] and GM[37]) inflammatory responses to pathogens or allergens. Although relatively high doses of LPS were used in the ex vivo culture system, this must be tempered by knowledge of the bio-availability of LPS in vivo. Physiologically, the fetus is exposed in vivo to LPS, because Gram-negative bacteria and associated LPS can be isolated from amniotic fluid in median concentrations of 0·05 μg/ml.[41] Though the minimal concentration of biologically

active LPS present within the intrauterine environment is unknown, soluble factors (e.g. sCD14) can modulate immune cell responses to LPS at 1000-fold lower concentrations than those observed in amniotic fluid.[42] The LPS concentration that we used in the current studies is in line with other in vitro progenitor cell studies,[12, 13] which have found minimal progenitor cell responses to LPS below 10 μg/ml. In addition, Roy et al.[43] have demonstrated that endotoxin levels range between 1 and 6 μg/g house dust in rural and urban homes. Hence, the dose of LPS used here appears to be in the physiological range of natural LPS exposure. We cannot conclude without addressing a couple of limitations of this study.

Levels of CD44 expressed on OVA-specific Th2 cells were higher than those on OVA-specific Th1 cells, whereas expression levels of CD49d were similar between these Th1 and Th2 cells (Fig. 5A, Fig. S1). Furthermore, receptor activity of CD44 was higher on OVA-specific Th2 cells than Th1 cells (Fig. 5A, Fig. S1). CD44 consists of a numerous number of variant isoforms generated by alternative splicing of ten variant exons 19. To investigate the differential expression of CD44 isoforms on Th1 and

Th2 cells, the expression of representative transcript variant 1, 3, 5, and 6, as well Epigenetics Compound Library nmr as total CD44 was determined by quantitative real-time RT-PCR. In accordance with the surface expression of CD44 (Fig. 5A), mRNA levels of total CD44 and all its variants examined in this study were significantly

higher in Th2 cells than Th1 cells (Fig. 5B). We have demonstrated that HA-binding activity of CD44 is negatively regulated by its sialylation 20. Therefore, the expression of several sialidases in Th1 and Th2 cells was investigated. The expression of sialidases Neu1 and Neu3 was significantly higher in Th2 cells than Th1 cells (Fig. 5C). Therefore, relative potent activation and participation of CD44 in the accumulation of Th2 cells may be caused, at least in part, by higher expression of these sialidases. We then developed a Th1- and Th2-mediated airway inflammation model using the previously described methods 13. To investigate the role of CD44 in this model, anti-CD44 mAb, IM7 was injected with these in vitro-differentiated Autophagy Compound Library cost Th1 or Th2 cells, as compared with anti-CD49d mAb, PS2. In mice that underwent transfer of Th1 or Th2-polarized DO11.10 T cells, accumulation of antigen-specific T cells in the airway was detectable upon inhalation challenge with OVA (Fig. 6A). Subsequently, the migration of eosinophils, neutrophils, and

lymphocytes was significantly induced in both Th1- and Th2-cell-transferred mice. The migration of these cells was dependent on infused T cells and their specific antigen, because they failed to infiltrate the lungs of bovine serum albumin-challenged mice. Neither IM7 nor PS2 affected the infiltration of inflammatory cells into the lung Selleck Cobimetinib in Th1-transferred mice. On the other hand, IM7, but not PS2, suppressed antigen-induced accumulation of lymphocytes in Th2-transferred mice (p=0.0494). Interestingly, infiltration of Th2-polarized DO11.10 T cells, but not Th1-polarized DO11.10 T cells, into the lung was significantly suppressed by IM7 (p=0.009). PS2 treatment had no effect on the infiltration of these Th cells into the lung (Fig. 6A). These findings suggest that both Th1 and Th2 cells could migrate in the lung upon antigen challenge, though CD44 specifically participates in the accumulation of Th2 cells. Finally, we investigated the antigen-induced AHR in this Th1- or Th2-transferred model.

Genome-wide studies in human T cells have also characterized patterns associated with promoters, enhancers and other well-conserved genomic regulatory regions.[34-38] For example, at promoter regions, H3K4me3 exists as a double peak immediately upstream of transcriptional start sites because of nucleosome depletion or Pol II binding.[34, 37, 39-42] In contrast, enhancers are characterized by the three H3K4 methylation states as well as the histone variant, H2A.Z in human T cells.[34, 38, 41] Bioinformatics analysis on 21 histone modifications in CD4+

T cells MK-1775 datasheet was used to classify genomic regions based on their regulatory functions. The study identified 14 distinct clusters of chromatin signatures for promoters.[43] A similar bioinformatics approach learn more separated 51 functionally distinct chromatin states

by using 38 histone modifications, Pol II and the insulator binding protein, CTCF (CCCTC-binding Factor). These chromatin states could be further categorized into five broad classes, namely promoter-associated states, transcription-associated states, active intergenic states, large-scale repressed states and repetitive states.[44] In addition, CpG islands have been linked with active marks like histone acetylation and H3K4me3 both in human T cells and embryonic stem cells.[35, 36, 45] Collectively, these distinct histone modifications specific to regional domains contribute to functional differences in gene regulation. Given the distinct chromatin states that govern specific regions of the genome, it is likely that genes with comparable transcription profiles

possess similar epigenetic landscapes. Genome-wide studies in human Liothyronine Sodium T cells have extensively characterized a large number of histone modifications using chromatin immunoprecipitation assays (ChIP) combined with massively parallel sequencing (ChIP-Seq) and have been particularly informative in identifying modification patterns associated with active and inactive genes.[34-38, 46, 47] In general, promoters with an active chromatin signature have intermediate to high gene expression levels but genes with low expression levels are associated with promoters with repressed chromatin signatures.[43] A major study focusing on 37 histone acetylation and methylation marks in human CD4+ T cells has shown that genes with different basal expression levels are associated with specific combinations of histone modifications.[38] A common backbone of histone modifications consisting of: histone variant H2A.Z, H2BK5ac, H2BK12ac, H2BK20ac, H2BK120ac, H3K4ac, H3K4me1, H3K4me2, H3K4me3, H3K9me1, H3K18ac, H3K27ac, H3K36ac, H4K5ac, H4K8ac, H4K91ac and H3K9ac was identified at a large number of promoters and tended to correlate with higher expression levels.

Activating NK cell receptors frequently transmit activating signals via immunoreceptor tyrosine-based activation motifs (ITAMs) present in accessory proteins non-covalently associated with the intracellular region of the activating receptor [17]. Activating NK cell receptors employing this strategy typically express a short cytoplasmic tail lacking ITIMs or other tyrosine signalling motif and possess a basic residue within their transmembrane sequence for association with transmembrane accessory proteins [10, 18, 19]. LLT1 possesses these properties associated with an activating receptor. In the present study, we have examined the signalling pathways

associated with LLT1-stimulated MLN8237 purchase IFN-γ production. We determined that the human NK cell line NK92 expresses LLT1 on its surface, and upon ligation with CD161 expressing K562 target cells stimulates IFN-γ production. Using this LLT1:CD161 ligation system, we analysed IFN-γ production in the presence or absence of specific pharmacological inhibitors to determine what signalling pathways are required for LLT1-induced IFN-γ production. These results indicate that LLT1 downstream signalling is likely dependent upon Src-protein tyrosine kinase [Src-PTK], p38 and ERK signalling pathways, but not dependent upon PKC, PI3K or calcineurin. These results were followed up with phosphorylation analysis, which confirmed that the ERK signalling pathway

is associated with Adriamycin nmr LLT1-mediated IFN-γ production. Finally, we analysed IFN-γ mRNA transcription associated with LLT1 ligation. We found that LLT1 ligation is not associated with any change oxyclozanide in detectable IFN-γ mRNA levels, suggesting that LLT1 stimulates IFN-γ production by modulating post-transcriptional or translational events. Tissue culture.  NK92 cells were maintained using alpha-MEM

(Hyclone, Logan, UT, USA) with 25% defined Foetal Bovine Serum (Hyclone, Logan, UT, USA) and where appropriate 30 U/ml recombinant human IL-2 (Calbiochem, La Jolla, CA, USA). All other cells were maintained using 4+RPMI 1640 (GibcoBRL, Grand Island, NY, USA; with 10 mm MEM non-essential amino acids, 10 mm HEPES, 100 mm Sodium Pyruvate, 2 mm glutamine and penicillin/streptomycin) with 10% FetalPlex Animal Serum Complex (Gemini Bio-Products, Sacramento, CA, USA) at 37 °C, 5% CO2 in a water-jacketed tissue culture CO2 incubator. Flow cytometry.  To evaluate the surface expression of LLT1 on NK92, cells were stained with 5 μg of anti-human OCIL/LLT1 monoclonal antibody (R & D Systems, Minneapolis, MN, USA) and 10 μg of 4C7 mouse anti-human LLT1 monoclonal antibody (Abnova, Taipei, Taiwan) and a PE-conjugated goat anti-mouse IgG polyclonal secondary antibody. In order to confirm the lack of CD161 expression on NK92 cells, cells were stained with mouse anti-human CD161 (Clone DX12; BD Biosciences, San Diego, CA, USA) and an FITC-conjugated goat anti-mouse IgG polyclonal secondary antibody.

In Experiment 3, familiarization to the place-of-articulation distinction was doubled to increase the amount of exposure, and in this case infants began discriminating the sounds. These results extend the processes of distributional learning to a new phonetic contrast, and reveal that at 10 months of age, distributional phonetic learning remains effective, but is more difficult than before perceptual reorganization. “
“Relations between maternal sensitivity and physiological reactivity

to infant crying were examined using measures of heart rate (HR) and respiratory sinus arrhythmia (RSA) in 49 mothers of second-born infants. Using the Ainsworth Sensitivity Scale, an independent assessment of maternal sensitivity was made during maternal free play and bathing of their infants. Physiological reactivity was measured while mothers listened to three blocks of infant cry sounds in a standard cry paradigm. Mothers scoring high on sensitivity were compared to less click here sensitive mothers on both their physiological reactivity to the presented crying sounds and their physiological mean-level differences. Significant interaction effects were found for both HR and RSA. Highly sensitive mothers showed a larger increase in HR and stronger RSA withdrawal in response to the first block of cry sounds compared to less sensitive mothers. Main effects showed that highly sensitive mothers had lower mean overall

HR, and higher mean RSA levels across all three blocks of crying sounds compared to less sensitive mothers. RSA withdrawal and accompanying HR increases are discussed Veliparib supplier from a polyvagal perspective as indicative of a Bacterial neuraminidase better capability in responding to infant signals of negative affect. “
“In a socially diverse sample of 206 infant–mother pairs, we investigated predictors of infants’ attachment security at 15 months, with a particular emphasis on mothers’ tendency to comment appropriately or in a non-attuned manner on their 8-month-olds’ internal states (so-called mind-mindedness).

Multinomial logistic regression analyses showed that higher scores for appropriate mind-related comments and lower scores for non-attuned mind-related comments distinguished secure-group mothers from their counterparts in the insecure-avoidant, insecure-resistant, and insecure-disorganized groups. Higher scores for appropriate mind-related comments and lower scores for non-attuned mind-related comments also independently predicted dichotomous organized/disorganized attachment. General maternal sensitivity predicted neither attachment security nor organization, although sensitivity was found to relate to dichotomous secure/insecure attachment specifically in the context of low socioeconomic status. The findings highlight how appropriate and non-attuned mind-related comments make independent contributions to attachment and suggest that mind-mindedness is best characterized as a multidimensional construct.