Determination of Poly(4,4′‐diphenylsulfonyl terephthalamide) Crystalline Structure Via WAXD and Molecular Simulations

The crystal structure of poly(4,4′‐diphenylsulfonyl terephthalamide) (pt‐PSA) is studied by X‐ray diffraction and molecular simulation. Although the number of observed reflections is limited to warrant a precise determination of the unit cell structure and symmetry, a reasonable monoclinic unit cell is suggested with dimensions of a = 0.645 nm, b = 0.488 nm, c = 3.010 nm, and γ = 122.5°. A twofold molecule with two monomeric units forming a large zigzag conformation satisfies the X‐ray diffraction data. A layer structure is formed in the crystal phase, which is stabilized by the hydrogen bond between ? NH and ? C?O and the parallel‐displaced π–π stacking from the distortional coplanarity of the benzene rings and amide group.

     

Novel MIR143‐NOTCH fusions in benign and malignant glomus tumors

Glomus tumors (GT) have been classified among tumors of perivascular smooth muscle differentiation, together with myopericytoma, myofibroma/tosis, and angioleiomyoma, based on their morphologic overlap. However, no molecular studies have been carried out to date to investigate their genetic phenotype and to confirm their shared pathogenesis. RNA sequencing was performed in three index cases (GT1, malignant GT; GT2, benign GT and M1, multifocal myopericytoma), followed by FusionSeq data analysis, a modular computational tool developed to discover gene fusions from paired‐end RNA‐seq data. A gene fusion involving MIR143 in band 5q32 was identified in both GTs with either NOTCH2 in 1p13 in GT1 or NOTCH1 in 9q34 in GT2, but none in M1. After being validated by FISH and RT‐PCR, these abnormalities were screened on 33 GTs, 6 myopericytomas, 9 myofibroma/toses, 18 angioleiomyomas and in a control group of 5 sino‐nasal hemangiopericytomas. Overall NOTCH2 gene rearrangements were identified in 52% of GT, including all malignant cases and one NF1‐related GT. No additional cases showed NOTCH1 rearrangement. As NOTCH3 shares similar functions with NOTCH2 in regulating vascular smooth muscle development, the study group was also investigated for abnormalities in this gene by FISH. Indeed, NOTCH3 rearrangements were identified in 9% of GTs, all present in benign soft tissue GT, one case being fused to MIR143. Only 1/18 angioleiomyomas showed NOTCH2 gene rearrangement, while all the myopericytomas and myofibroma/toses were negative. In summary, we describe novel NOTCH1–3 rearrangements in benign and malignant, visceral, and soft tissue GTs. © 2013 Wiley Periodicals, Inc.     

It takes two to talk: Longitudinal associations among infant–mother attachment,maternal attachment representations,and mother–child emotion dialogues

Research on the attachment-dialogue link has largely focused on infant–mother attachment. This study investigated longitudinal associations between infant–mother attachment and maternal attachment representations and subsequent mother–child emotion dialogues (N = 50). Maternal attachment representations were assessed using the Adult Attachment Interview when children were 3 months, infant–mother attachment was assessed using the Strange Situation Procedure at 13 months, and mother–child emotion dialogues were assessed using the Autobiographical Emotional Events Dialogue at 3.5 years. Consistent with past research, the three organized categories of infant–mother attachment relationships were associated with later mother–child emotion dialogues. Disorganized attachment relationships were associated with a lack of consistent and coherent strategy during emotion dialogues. Autonomous mothers co-constructed coherent narratives with their children; Dismissing and Preoccupied mothers created stories that were less narratively organized. Although the Unresolved category was unrelated to classifications of types of mother–child discourse, mothers’ quality of contribution to the dialogues was marginally lower compared to the quality of their children’s contributions to the emotion discussion. Secure children showed highest levels of child cooperation and exploration. Autonomous mothers displayed highest levels of maternal sensitive guidance during emotion dialogues. We provide preliminary evidence for role reversal in dialogues between Preoccupied and Unresolved mothers and their children.     

Anti-inflammatory effects of peptides from a marine algicolous fungus Acremonium sp. NTU492 in BV-2 microglial cells

Located in tropical and subtropical region, Taiwan is an island with high algal species diversity. In this study, a number of fungal strains were isolated from marine macroalgae collected from northeastern intertidal zone of Taiwan. Preliminary anti-inflammatory screening has shown that the methanolic extracts of solid fermented products of the red alga Mastophora rosea-derived fungal strain Acremonium sp. NTU492 exhibited significant bioactivity. In an attempt to disclose the active principles from this fungal strain, a series of separation and purification was thus undertaken, which has led to the isolation and characterization of seven compounds including four new peptides, namely acrepeptins A–D (1–4), along with previously reported destruxin B (5), guangomide A (6), and guangomide B (7). Their structures were elucidated by spectroscopic analysis and compared with literatures. Of these, acrepeptins A (1) and C (3) showed markedly inhibitory activities on nitric oxide production in lipopolysaccharide-activated microglial BV-2 cells with IC₅₀ values of 12.0 ± 2.3 and 10.6 ± 4.0 μM, respectively. Furthermore, acrepeptins A (1) and C (3) significantly attenuated the expression of inducible nitric oxide synthase in a concentration-dependent manner (5–40 μM).     

Myocardial tissue Doppler-based indexes to distinguish right ventricular volume overload from right ventricular pressure overload

The objective of this study was to develop tissue Doppler parameters that could be used to differentiate right ventricular (RV) volume overload from RV pressure overload. The RV-pressure-overload group consisted of 40 patients with severe pulmonary hypertension, and the RV-volume-overload group consisted of 40 patients who had an atrial septal defect without evidence of right-to-left shunt, significant pulmonary hypertension, or Eisenmenger's complex. Another 40 healthy subjects were enrolled and served as a control group. Routine echocardiography and tissue Doppler imaging were performed. RV myocardial performance index was determined based on data collected during tissue Doppler imaging over the lateral tricuspid annulus. In patients with RV pressure overload, tissue Doppler parameters showed characteristically lower systolic velocity over the tricuspid annulus (RV myocardial systolic wave [Sm]) and longer isovolumic relaxation time (RV-IVRT). Nevertheless, in patients with RV volume overload, RV-Sm increased significantly, but early-diastolic velocity over tricuspid annulus was relatively low. In conclusion, RV-MPI, RV-Sm/early-diastolic velocity over tricuspid annulus, and RV-IVRT/RV-Sm were all useful to differentiate RV pressure overload from volume overload, although RV-IVRT/RV-Sm was the best parameter, with excellent sensitivity and specificity.     

Massive Lower Gastrointestinal Hemorrhage Caused by a Large Extraluminal Leiomyoma of the Colon: Report of a Case

The occurrence of leiomyoma of the colon is uncommon. Most of these lesions are clinically silent and are found incidentally during laparotomy or endoscopic procedures for unrelated conditions. Symptomatic leiomyomas of the colon are encountered less frequently, with only sporadic reports in the literatures. We describe a heretofore unreported case of a large extraluminal leiomyoma of the sigmoid colon presenting as massive lower gastrointestinal hemorrhage. Because it was extraluminal in position, it was difficult to make an accurate diagnosis endoscopically and the condition was easily misdiagnosed as angiodysplasia of the colon until CT scan results were seen. Although rare and benign in nature, leiomyoma of the colon may cause life-threatening complications that require emergency surgery and should be included in the differential diagnosis of lower gastrointestinal hemorrhage.     

Increased urinary endothelin-1 excretion in newly diagnosed type 2 diabetic patients

To investigate whether urinary and plasma endothelin (ET)-1 concentrations are responsive to the alteration of intravascular blood volume in uncontrolled diabetic patients, we determined urinary ET-1 excretion and plasma ET-1 concentration in 42 newly diagnosed type 2 diabetic patients and 38 normal subjects. Mean fasting plasma glucose value (12.8 +/- 0.72 mmol l-1) and plasma renin activity (PRA, 2.80 +/- 0.44 ng ml-1 hr-1) in diabetic patients were significantly higher as compared to normal controls (mean plasma glucose value: 5.2 +/- 0.83 mmol l-1; mean PRA value: 1.34 +/- 0.17 ng ml-1 hr-1), whereas plasma ET-1 value (1.33 +/- 0.07 pmol l-1) was not significantly different from that (1.29 +/- 0.06 pmol l-1) of normal controls. Mean urinary ET-1 excretion level (7.53 +/- 0.74 nmol mol-1 creatinine) was significantly higher than that (5.36 +/- 0.37 nmol mol-1 creatinine) of normal controls. Urinary ET-1 excretion was correlated with plasma glucose value (r = 0.360, p < 0.05) and PRA value (r = 0.381, p < 0.05). Urinary ET-1 excretion rate (5.17 +/- 0.37 nmol mol-1 creatinine) and PRA value (1.42 +/- 0.18 ng ml-1 hr-1) declined to normal levels when mean plasma glucose value decreased to the level of 7.1 +/- 0.39 mmol l-1 in diabetic patients after 4 months of glycemic control. Our results indicated that renal-derived ET-1 was responsive to the alteration of intravascular blood volume in untreated newly diagnosed type 2 diabetic patients.     

Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity

The cancer stem cells (CSCs) of glioblastoma multiforme (GBM), a grade IV astrocytoma, have been enriched by the expressed marker CD133. However, recent studies have shown that CD133⁻ cells also possess tumor-initiating potential. By analysis of gangliosides on various cells, we show that ganglioside D3 (GD3) is overexpressed on eight neurospheres and tumor cells; in combination with CD133, the sorted cells exhibit a higher expression of stemness genes and self-renewal potential; and as few as six cells will form neurospheres and 20–30 cells will grow tumor in mice. Furthermore, GD3 synthase (GD3S) is increased in neurospheres and human GBM tissues, but not in normal brain tissues, and suppression of GD3S results in decreased GBM stem cell (GSC)-associated properties. In addition, a GD3 antibody is shown to induce complement-dependent cytotoxicity against cells expressing GD3 and inhibition of GBM tumor growth in vivo. Our results demonstrate that GD3 and GD3S are highly expressed in GSCs, play a key role in glioblastoma tumorigenicity, and are potential therapeutic targets against GBM.Glioblastoma multiforme (GBM) is extremely infiltrative and difficult to treat, and most patients develop recurrence after therapy. Over the past decade, many studies have suggested that bulk GBM tumors harbor cancer stem cells (CSCs) (1, 2), a distinct subpopulation of cancer cells that are able to initiate new tumors efficiently, have long-term self-renewal capacity, and survive better against chemo- or radiotherapy (2–4). CD133 has become a widely used marker for the enrichment of GBM CSCs (GSCs) and other tumor types (5–10). However, recent studies have shown that CD133 is not specific for GSCs because CD133⁻ cells also possess tumor-initiating potential (11–13), indicating the need to identify more specific and exclusive markers for GSCs to facilitate our understanding of GSCs and therapeutic development against GBM. Several reports have proposed L1CAM, A2B5, integrin α6, MET, and CD15 as markers for GSCs (14–18). However, none of these protein markers could be used specifically to identify GSCs, and no study was reported with respect to glycans as potential markers, although glycan biosynthesis involves multiple genes and it is possible to create different structures in cancer progression. It is noted that ganglioside D2 (GD2) and ganglioside D3 (GD3) were found on the surface of neural stem cells (NSCs) and that stage-specific embryonic antigen 3 (SSEA3) and SSEA4 were found on embryonic stem cells and cancer cells (19–21), but there is no glycan marker found on the surface of GSCs.Gangliosides are sialic acid-containing glycosphingolipids (GSLs) that are most abundant in the nervous system (22). The expression levels and patterns of gangliosides during brain development shift from simple gangliosides, such as GM3 and GD3, to complex gangliosides, such as GM1, GD1a, GD1b, and GT1b (23, 24). Moreover, several unique ganglioside markers, including SSEA3, SSEA4, GD2, and GD3, have been identified in stem cells (19). GD3, a b-series ganglioside containing two sialic acids, is highly expressed in mouse and human embryonic NSCs (20, 25). In cancers, GD3 is highly accumulated in human primary melanoma tissues as well as in established melanoma cell lines (26), whereas human normal melanocytes express no or minimal levels of GD3 (27). Moreover, malignant gliomas contain higher levels of GD3, and its expression correlates with the degree of malignancy (28). GD3 is produced from the precursor GM3 by the activity of GD3 synthase (GD3S), which mediates the properties of CSCs through the c-MET signaling pathway and correlates with poor prognosis in triple-negative human breast tumors (29). These findings suggest that GD3 may play an important role in the transformation of normal cells into tumors, and imply that GD3 could be a cell surface marker for GSCs.This study was designed to identify glycan markers for the enrichment of GBM stem cells and then uses these enriched GBM stem cells to characterize tumorigenicity, their association with clinical GBM specimens, and their regulation in tumor progression. The results showed that GD2 and GD3 were positively stained on GBM neurospheres. We found that cells with high GD3 expression display functional characteristics of GSCs. Suppression of GD3S, a critical enzyme for GD3 synthesis, impeded neurosphere formation and tumor initiation. The expression of GD3S correlated with the grades of astrocytomas and mediated self-renewal through c-Met activation. Furthermore, a GD3 antibody was found to eliminate the GD3⁺ cells through complement-dependent cytotoxicity (CDC) in vitro and to suppress tumor growth in mice. These results suggest that GD3 could be a significant biomarker for GSCs, that CD3 could be combined with CD133 for the enrichment of GSCs, and that both GD3 and GD3S could be targets for the development of new therapies against GBM.