Miracle-dz/UniFAR-FTUs huggingface dataset:
Association study in a South Indian population supports rs1015213 as a risk factor for primary angle closure.

PURPOSE Three loci defined by single nucleotide polymorphisms (SNPs) rs11024102 in PLEKHA7, rs3753841 in COL11A1, and rs1015213 between the PCMTD1 and ST18 genes, recently have been associated with primary angle closure glaucoma (PACG). We explored the genetic association of these SNPs with subtypes of primary angle closure in a South Indian population. METHODS The study included three case definitions: primary angle closure/primary angle closure glaucoma (PAC/PACG, N = 180); primary angle closure suspect (PACS, N = 171), and a combined any-angle closure group. Controls consisted of 411 individuals from South India. Genotyping for all three SNPs was performed using the TaqMan allelic discrimination assay. Genetic association was estimated using a χ(2) test statistics and logistic regression. RESULTS Among the three studied SNPs, significant genetic association was identified for rs1015213 in the PAC/PACG (P = 0.002) and any-angle closure (P = 0.003) analyses. However, no significant genetic association was seen when in PACS subjects (P = 0.052). SNPs rs3753841 and rs11024102 showed no evidence of genetic association with angle-closure phenotypes (P > 0.05) in South Indian participants. CONCLUSIONS In our study, rs1015213 (located in the intergenic region between PCMTD1 and ST18) was associated significantly with PAC/PACG, confirming prior reports of an association between this region and angle closure glaucoma. Further work with a larger sample size is necessary to confirm the importance of COL11A1 and PLEKHA7 in the pathogenesis of glaucoma.
Resolving Semantic Ambiguities in Sentences: Cognitive Processes and Brain Mechanisms

Functional MRI studies of how the brain processes sentences containing semantically ambiguous words have consistently implicated (i) the left inferior frontal gyrus (LIFG) and (ii) posterior regions of the left temporal lobe in processing high-ambiguity sentences. This article reviews recent findings on this topic and relates them to (i) psycholinguistic theories about the underlying cognitive processes and (ii) general neuro-cognitive accounts of the relevant brain regions. We suggest that the LIFG plays a general role in the cognitive control processes that are necessary to select contextually relevant meanings and to reinterpret sentences that were initially misunderstood, but it is currently unclear whether these control processes should best be characterised in terms of specific processes such as conflict resolution and controlled retrieval that are required for high-ambiguity sentences, or whether its function is better characterised in terms of a more general set of ‘unification’ processes. In contrast to the relatively rapid progress that has been made in understanding the function of the LIFG, we suggest that the contribution of the posterior temporal lobe is less well understood and future work is needed to clarify its role in sentence comprehension.
Expression of Cytoplasmic Islet Cell Antigens by Rat Pancreas

A major problem in standardization of the islet cell cytoplasmic antibody (ICA) assay is variation in sensitivity of the different human pancreas substrates used in individual laboratories. To circumvent this problem, we have developed an assay that utilizes Wistar-Furth rat pancreas as substrate, an anti-islet monoclonal antibody (A2B5) to identify islets and fluorescein-conjugated protein A to identify patient autoantibodies. Sera from 85 control subjects, 27 type I diabetics, and 17 subjects at high risk for developing type I diabetes were assayed in parallel with our standard ICA assay on human pancreas substrate and with Wistar-Furth rat pancreas as substrate. Two sera from control subjects (2 of 85) were ICA positive with rat pancreas compared to 1 of 85 with human pancreas substrate. Sera from 11 of 27 type I diabetics and 15 of 17 sera from high-risk subjects were ICA positive with either rat or human pancreas substrate. A correlation between the specific islet fluorescence readings on human and rat pancreas sections was found with sera from high-risk and control subjects. Furthermore, end-point titers of an ICA-positive serum were identical with both assays. Finally, incubation of an ICA-positive serum with glycolipids, extracted from either human or Wistar-Furth rat pancreas, blocked subsequent ICA binding. These findings suggest that Wistar-Furth rat pancreas expresses an identical or similar autoantigen to human pancreas.
Near field optical microscopy in aqueous solution: implementation and characterization of a vibrating probe

Near field optical microscopy (NSOM) is one of the possible solutions to circumvent the diffraction limit, but the control of the optical probe in solution has been a technical challenge for practical applications. Most recently, it has been shown that the pipette used in the scanning ion conductance microscope can be modified to form a high resolution near field optical probe. When combined with a novel distance modulation mechanism, a robust near field microscope can be constructed for operation in aqueous solution. In this paper, we present technical details of this design and a further characterization of the NSOM system for imaging in solution. Fundamental limitations of this approach in comparison to other systems are also discussed. Based on the current technology, it is concluded that better than 50 nm resolution should be achievable with this technique for fluorescence, as well as fluorescence resonance energy transfer, imaging of biological specimens.
Is direct coronary stenting the best strategy for long-term outcome? Results of the multicentric randomized benefit evaluation of direct coronary stenting (BET) study.

BACKGROUND Preliminary trials of direct coronary stenting have demonstrated the benefits of this approach. It lowers procedural cost, time, and radiation exposure compared with predilatation. Nevertheless, the long-term outcome after direct stenting remains less well known. METHODS Between January and September 1999, 338 patients were randomly assigned to either direct stent implantation (DS+, n = 173) or standard stent implantation with balloon predilatation (DS-, n = 165). Clinical follow-up was performed. RESULTS Baseline characteristics were similar in the 2 groups. Procedural success was achieved in 98.3% of patients assigned to DS+ and 97.5% of patients assigned to DS- (not significant). Clinical follow-up was obtained in 99% of patients (mean 16.4 +/- 4.6 months). Major adverse cardiac events--defined as whichever of the following occurred first; cardiac death, myocardial infarction, unstable angina, new revascularization--were observed at a higher rate in the DS+ group than in the DS-, but this difference was not significant (11.3% vs 18.2%, P = not significant). The difference in target lesion revascularization rate in the DS+ group (7%) and DS- group (5.2%) was also not significant. Multivariate analysis showed that direct stenting had no influence on long-term major adverse cardiac events rate. Independent relationships were found between long-term major adverse cardiac events rate and final minimal lumen diameter <2.48 mm (relative risk [RR] 0.449, CI 0.239-0.845, P =.013), prior myocardial infarction (RR 2.028, CI 1.114-3.69, P =.02), and hypertension (RR 1.859, CI 1.022-3.383, P =.042). CONCLUSION The main finding that emerges from this randomized study is that the influence of direct stenting on long-term need for new target lesion revascularization does not differ from that of stenting with balloon predilatation.
Contribution of No‐reflow phenomenon to hepatic injury after ischemia‐reperfusion: Evidence for a role for superoxide anion

Controversy exists as to the role of oxygen‐derived free radicals in tissue injury and the no‐reflow phenomenon in reperfusion injury after ischemia. In this study using an experimental rat model, left hepatic lobar ischemia followed by reperfusion resulted in an increase of serum glutamic pyruvic transaminase at 30 min with concomitant histological evidence of hepatocellular necrosis at 24 hr. In the in vivo liver microcirculation, reperfusion after ischemia resulted in an initial transient return of blood flow, but stasis of blood flow later developed in the liver sinusoids. Thus a no‐reflow phenomenon in the microcirculation was demonstrated. Intravenous administration of a longacting form of superoxide dismutase (half‐life 6 hr, dose 4 or 8 mg/kg) significantly decreased the hepatocellular necrosis and reduced the microcirculatory stasis in the liver sinusoids. These studies established the important contribution of the no‐reflow phenomenon in ischemia‐reperfusion injury to the liver and the participation of superoxide anions in mediating the no‐reflow phenomenon.
Effects of estradiol and progesterone on the cytodifferentiation of epithelial cells in the oviduct of the newborn golden hamster

The effects of estradiol and progesterone on the cytodifferentiation of epithelial cells in the oviduct of the newborn golden hamster were investigated by electron microscopy. Consecutive daily injections of estradiol‐17β (E2) induced various ultrastructural changes in undifferentiated epithelial cells of the neonatal oviduct. Ciliogenesis, formation of some ciliary buds, and ciliation were frequently observed in the oviductal epithelial cells on days 1–4 of consecutive treatments with E2. On days 2 and 3, the remaining cells contained well‐developed Golgi apparatus and rough endoplasmic reticulum. Thereafter, a few secretory granules were observed in the cytoplasm of these cells, indicative of differentiation into secretory cells. Occasionally, secretory cells undergoing ciliogenesis or mitosis were found in the epithelium. On day 9, many fully mature ciliated and secretory cells were observed. Quantitative studies clearly showed that E2 induced the differentiation of both ciliated and secretory cells. By contrast, consecutive daily injections of progesterone significantly stimulated the appearance of ciliogenic and ciliated cells but not that of secretory cells. These results indicate that the induction of differentiation of secretory cells is a specific effect of estrogen, whereas the differentiation of ciliated cells may be closely related to effect of progesterone as well as of estrogen. It is suggested that hormonal effects on differentiation differ between ciliated and secretory cells in the oviductal epithelium of the newborn golden hamster. © 1993 Wiley‐Liss, Inc.
Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia

Linkage analyses suggest that chromosome 22q12‐13 may harbor a shared susceptibility locus for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of a sample from the Faeroe Islands we have previously reported association between both disorders and microsatellite markers in a 3.6 cM segment on 22q13. The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Nine SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: an extension of the previously analyzed Faeroese sample comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ, and 200 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample overall P‐values of 0.0009, 0.0054, and 0.0023 were found for haplotypes in BPD, SZ, and combined cases, respectively, and in the Scottish sample overall P‐values of 0.0003, 0.0005, and 0.016 were observed for similar groupings. Specific haplotypes showed associations with lowest P‐values of 7 × 10−5 and 0.0006 in the combined group of cases from the Faeroe Islands and Scotland, respectively. The G protein‐coupled receptor 24 encoded by GPR24 binds melanin‐concentrating hormone (MCH) and has been implicated with feeding behavior, energy metabolism, and regulation of stress and mood. To our knowledge this is the first study reporting association between GPR24 and BPD and SZ, suggesting that GPR24 variants may confer susceptibility to both disorders. © 2006 Wiley‐Liss, Inc.
Early information processing biases in social anxiety

Considerable controversy persists regarding the nature of threat-related attention biases in social anxiety. Previous studies have not considered how variations in the temporal and energetic dimensions of affective stimulus delivery interact with anxiety-related individual differences to predict biased attention. We administered a visual dot-probe task, using faces that varied in affective intensity (mild, moderate, strong) and presentation rate (100, 500, 1,250 ms) to a selected sample. The high, compared to the low, socially anxious group showed vigilance towards angry faces and emotionally ambiguous faces more generally during rapid (100 ms) presentations. By 1,250 ms, there was only a non-specific motor slowing associated with angry faces in the high socially anxious group. Findings suggest the importance of considering both chronometric and energetic dimensions of affective stimuli when examining anxiety-related attention biases. Future studies should consider using designs that more closely replicate aspects of real-world interaction to study processing biases in socially anxious populations.
Dysfunctional mitochondrial fission impairs cell reprogramming

ABSTRACT We have recently shown that mitochondrial fission is induced early in reprogramming in a Drp1-dependent manner; however, the identity of the factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used a panel of RNAi targeting factors involved in the regulation of mitochondrial dynamics and we observed that MiD51, Gdap1 and, to a lesser extent, Mff were found to play key roles in this process. Cells derived from Gdap1-null mice were used to further explore the role of this factor in cell reprogramming. Microarray data revealed a prominent down-regulation of cell cycle pathways in Gdap1-null cells early in reprogramming and cell cycle profiling uncovered a G2/M growth arrest in Gdap1-null cells undergoing reprogramming. High-Content analysis showed that this growth arrest was DNA damage-independent. We propose that lack of efficient mitochondrial fission impairs cell reprogramming by interfering with cell cycle progression in a DNA damage-independent manner.
Why Are Some Individuals Not Racially Biased?

Two studies investigated the psychological underpinnings of racial nonbias, defined as extremely low or null bias on measures of implicit and explicit racial attitudes. In Study 1, racially nonbiased Whites showed differential susceptibility to affective conditioning compared with subjects with greater bias. A significant two-way interaction emerged, indicating that nonbiased individuals were significantly less likely than other individuals to acquire negative affective associations to neutral stimuli in a classical conditioning paradigm, but were more likely than other individuals to acquire positive affective associations to neutral stimuli. This pattern of findings was replicated in Study 2, in which the identification of nonbiased Whites was facilitated by their nomination by an African American acquaintance. Implications for bias formation and prejudice reduction are discussed.
Multiphase ECG‐triggered 3D contrast‐enhanced MR angiography: Utility for evaluation of hilar and mediastinal invasion of bronchogenic carcinoma

The purpose of this study was to evaluate the usefulness of cardiac synchronized magnetic resonance angiography [electrocardiographically (ECG)‐triggered MRA] for improving image quality and detection of hilar and mediastinal invasion of bronchogenic carcinoma. Fifty patients, suspected of having hilar or mediastinal invasion of bronchogenic carcinoma, underwent contrast‐enhanced computed tomography and MR imaging including conventional and ECG‐triggered MRA. Twenty patients subsequently also underwent surgical resection. Vascular enhancement‐to‐background ratio (VBR), vascular enhancement‐to‐tumor ratio (VTR), signal‐to‐noise ratio (SNR), contrast‐to‐noise ratio (CNR) and image quality scores of thoracic vessels obtained with both MRA techniques were determined and compared. In addition, the diagnostic accuracy of tumor invasion of pulmonary vessels was compared. VBRs and VTRs of both MRA techniques were not significantly different. ECG‐triggered MRA significantly improved SNRs and CNRs (P < 0.05). Two readers judged that overall image quality of ECG‐triggered MRA was better than that of conventional MRA (κ ≥ 0.41). In conclusion, ECG‐triggered MRA improves the image quality and the detection of hilar and mediastinal invasion of bronchogenic carcinoma. J. Magn. Reson. Imaging 2001;13:215–224. © 2001 Wiley‐Liss, Inc.
The intrinsically disordered TC‐1 interacts with Chibby via regions with high helical propensity

Thyroid cancer 1 (TC‐1) is a 106‐residue naturally disordered protein that has been found to associate with thyroid, gastric, and breast cancers. Recent studies showed that the protein functions as a positive regulator in the Wnt/β‐catenin signaling pathway, a pathway that is known to play essential roles in developmental processes and causes tumor formation when misregulated. By competing with β‐catenin for binding to Chibby (Cby), a conserved nuclear protein that antagonizes the β‐catenin–mediated transcriptions, TC‐1 up‐regulates a number of β‐catenin target genes that are known to be involved in the aggressive behavior of cancers. In order to gain a molecular understanding of the role TC‐1 plays in regulating the Wnt/β‐catenin signaling pathway, detailed structural studies of the protein and its interaction with Cby are essential. In this work, we used nuclear magnetic resonance (NMR) spectroscopy to elucidate the structure of TC‐1 and its interaction with Cby. Our results indicate that even though TC‐1 is naturally disordered, the protein adopts fairly compact conformations under nondenaturing conditions. Chemical shift analysis and relaxation measurements show that three regions (D44‐R53, K58‐A64, and D73‐T88) with high‐helical propensity are present in the C‐terminal portion of TC‐1. Upon addition of Cby, significant broadening of resonance signals derived from these helical regions of TC‐1 was observed. The result indicates that the intrinsically disordered TC‐1 interacts with Cby via its transient helical structure.
Loss of p27Kip1 but not p21Cip1 decreases survival and synergizes with MYC in murine lymphomagenesis

The cyclin‐dependent kinase (CDK) inhibitors p21Cip1 and p27Kip1 are induced in response to anti‐proliferative stimuli and block G1/S‐phase progression through the inhibition of CDK2. Although the cyclin E–CDK2 pathway is often deregulated in tumors the relative contribution of p21Cip1 and p27Kip1 to tumorigenesis is still unclear. The MYC transcription factor is an important regulator of the G1/S transition and its expression is frequently altered in tumors. Previous reports suggested that p27Kip1 is a crucial G1 target of MYC. Our study shows that in mice, deficiency for p27Kip1 but not p21Cip1 results in decreased survival to retrovirally‐induced lymphomagenesis. Importantly, in such p27Kip1 deficient lymphomas an increased frequency of Myc activation is observed. p27Kip1 deficiency was also shown to collaborate with MYC overexpression in transgenic lymphoma models. Thus, in vivo, the capacity of MYC to promote tumor growth is fully retained and even enhanced upon p27Kip1 loss. We show that in lymphocytes, MYC overexpression and p27Kip1 deficiency independently stimulate CDK2 activity and augment the fraction of cells in S phase, in support of their distinct roles in tumorigenesis.
Absorption and retention of nickel from drinking water in relation to food intake and nickel sensitivity.

Two studies were performed to examine the influence of fasting and food intake on the absorption and retention of nickel added to drinking water and to determine if nickel sensitization played any role in this regard. First, eight nonallergic male volunteers fasted overnight before being given nickel in drinking water (12 micrograms Ni/kg) and, at different time intervals, standardized 1400-kJ portions of scrambled eggs. When nickel was ingested in water 30 min or 1 h prior to the meal, peak nickel concentrations in serum occurred 1 h after the water intake, and the peak was 13-fold higher than the one seen 1 h after simultaneous intake of nickel-containing water and scrambled eggs. In the latter case, a smaller, delayed peak occurred 3 h after the meal. Median urinary nickel excretion half-times varied between 19.9 and 26.7 h. Within 3 days, the amount of nickel excreted corresponded to 2.5% of the nickel ingested when it was mixed into the scrambled eggs. Increasing amounts were excreted as the interval between the water and the meal increased, with 25.8% of the administered dose being excreted when the eggs were served 4 h prior to the nickel-containing drinking water. In the second experiment, a stable nickel isotope, 61Ni, was given in drinking water to 20 nickel-sensitized women and 20 age-matched controls, both groups having vesicular hand eczema of the pompholyx type. Nine of 20 nickel allergic eczema patients experienced aggravation of hand eczema after nickel administration, and three also developed a maculopapular exanthema. No exacerbation was seen in the control group. The course of nickel absorption and excretion in the allergic groups did not differ and was similar to the pattern seen in the first study, although the absorption in the women was less. A sex-related difference in gastric emptying rates may play a role. Thus, food intake and gastric emptying are of substantial significance for the bioavailability of nickel from aqueous solutions.
Relationships between Root Temperature and the Transport of Ammonium and Nitrate Ions by Italian and Perennial Ryegrass (Lolium multiflorum and Lolium perenne).

At root temperature below 14 C the absorption of (15)N from NH(4) (+) greatly exceeded that from NO(2) (-) by tillers of Lolium multiflorum and Lolium perenne under conditions where pH, external concentration, plant N status, and pretreatment temperature were varied. There was a marked increase in the temperature sensitivity of NO(3) (-) transport below 14 C, irrespective of the temperature at which plants were grown previously. A marked increase in the temperature sensitivity was also seen for NH(4) (+) transport, but this occurred at the lower temperature of 10 C. Pretreatment of roots at 8 C lowered this still further to 5 C. Above and below these transition temperatures the Q(10) values for NO(3) (-) and NH(4) (+) transport were similar. Thus, the increased absorption of NH(4) (+) relative to NO(3) (-) at low temperatures seems to be related primarily to the difference in transition temperatures.It seems possible that NO(3) (-) and NH(4) (+) are absorbed through separate regions of the cell membrane differing in lipid composition and phase transition temperatures.