Miracle-dz/UniFAR-FTUs huggingface dataset:
1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one inhibits neurite outgrowth and causes neurite retraction in PC12 cells independently of soluble guanylyl cyclase

The effect of the potent soluble guanylyl cyclase (sGC) inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) on neurite outgrowth and retraction was investigated in PC12 cells and SH‐SY5Y human neuroblastoma cells. ODQ inhibited neurite outgrowth and triggered neurite retraction in the cells stimulated with nerve growth factor (NGF), staurosporine, or Y‐27632. The nitric oxide (NO) scavenger 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethyl‐imidazoline‐1‐oxyl‐3‐oxide (PTIO) had little effect on neurite outgrowth induced by Y‐27632 or staurosporine. In the presence of ODQ, treatment of the cells with the cell‐permeable cGMP analogue 8‐bromo‐cGMP failed to retrigger Y‐27632‐ and staurosporine‐induced neurite outgrowth. Furthermore, the depletion of sGC by RNA interference failed to prevent Y‐27632‐ and staurosporine‐induced neurite outgrowth. These results indicate that the NO/sGC/cGMP signaling cascade is not critically involved in ODQ‐induced neurite remodeling. The MEK inhibitor PD98059 did not inhibit neurite outgrowth, and Y‐27632 and staurosporine did not induce ERK phosphorylation, suggesting that the inhibitory effect of ODQ on neurite outgrowth is independent of the ERK signaling pathway. In contrast, pretreatment with dithionite or a hemin‐glutathione mixture reversed the inhibitory effect of ODQ on Y‐27632‐ and staurosporine‐induced neurite outgrowth, indicating that ODQ might act on an intracellular redox‐sensitive molecule. We conclude that ODQ inhibits Y‐27632‐ and staurosporine‐induced neurite outgrowth and triggers neurite retraction in an sGC‐independent manner in neuronal cells and suggest that oxidation of unidentified redox‐sensitive protein could be responsible for these effects. © 2008 Wiley‐Liss, Inc.
Posttraumatic stress and depressive reactions among Nicaraguan adolescents after hurricane Mitch.

OBJECTIVE This study determined the severity of posttraumatic stress and depressive reactions among Nicaraguan adolescents after Hurricane Mitch and the relationship of these reactions to objective and subjective features of hurricane exposure, death of a family member, forced relocation, and thoughts of revenge. METHOD Six months after the hurricane, 158 adolescents from three differentially exposed cities were evaluated by using a hurricane exposure questionnaire, the Child Posttraumatic Stress Disorder Reaction Index, and the Depression Self-Rating SCALE: RESULTS Severe levels of posttraumatic stress and depressive reactions were found among adolescents in the two most heavily affected cities. Severity of posttraumatic stress and depressive reactions and features of objective hurricane-related experiences followed a "dose-of-exposure" pattern that was congruent with the rates of death and destruction across cities. Level of impact (city), objective and subjective features, and thoughts of revenge accounted for 68% of the variance in severity of posttraumatic stress reaction. Severity of posttraumatic stress reaction, death of a family member, and sex accounted for 59% of the variance in severity of depression. CONCLUSIONS After a category 5 hurricane, adolescents in heavily affected areas with extreme objective and subjective hurricane-related traumatic features of exposure experience severe and chronic posttraumatic stress and comorbid depressive reactions. The recovery of the severely affected Nicaraguan adolescents is vital to the social and economic recovery of a country ravaged by years of political violence and poverty. These findings strongly indicate the need to incorporate public mental health approaches, including systematic screening and trauma/grief-focused interventions, within a comprehensive disaster recovery program.
QoS aware relay selection and subcarrier allocation in cooperative OFDMA systems

Most existing works on resource allocation in cooperative OFDMA systems have focused on homogeneous users with same service and demand. In this letter, we investigate relay selection and subcarrier allocation in a cooperative OFDMA system with considerations of QoS guarantees and service support. By introducing QoS price, this combinatorial problem with exponential complexity is converted into a convex one, and a dual based QoS-aware schedule (QAS) algorithm is proposed to tackle the problem. Simulation results reveal that our proposed algorithm significantly outperforms previous works in terms of both services support and QoS satisfaction.
Caudate Volume in Offspring at Ultra High Risk for Alcohol Dependence: COMT Val158Met, DRD2, Externalizing Disorders, and Working Memory.

BACKGROUND There is emerging evidence that the increased susceptibility to developing alcohol and substance use disorders in those with a family history of Alcohol Dependence (AD) may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing. Externalizing disorders of childhood including Attention Deficit Hyperactivity Disorder, Conduct and Oppositional Disorders are a prominent feature of those with a positive family history. The caudate nuclei have been implicated in both the salience of rewards and in the pathophysiology of alcohol dependence and these often antecedent childhood disorders. METHODS Adolescent/young adult high and low-risk for AD offspring (N = 130) were studied using magnetic resonance imaging. Volumes of the caudate nucleus were obtained using manual tracing with BRAINS2 software and neuropsychological functioning determined. Childhood disorders were assessed as part of a long-term longitudinal follow-up that includes young adult assessment. Dopaminergic variation was assessed using genotypic variation in the catechol-O-methyltransferase (COMT) and DRD2 genes. RESULTS High-risk subjects showed poorer Working Memory functioning. Cau-date volume did not differ between high and low-risk subjects, but those with externalizing disorders of childhood showed reduced caudate volume. Variation in COMT and DRD2 genes was associated with Working Memory performance and caudate volume. CONCLUSIONS Caudate volume is reduced in association with externalizing disorders of childhood/adolescence. Working Memory deficits appear in familial high-risk offspring and those with externalizing disorders of childhood. The dopaminergic system appears to be involved in both working memory performance and externalizing disorders of childhood.
Conjugation Reactions in the Newborn Infant: The Metabolism of Para-aminobenzoic Acid

It has been shown that the liver of the newborn infant has a limited capacity to perform certain transformation or conjugation reactions when compared to older subjects (Driscoll and Hsia, 1958; Kretchmer, Levine, McNamara, and Barnett, 1956). This limitation is evident in the formation of glucuronides (Brown and Zuelzer, 1958; Vest, 1958) and plays an important role in the genesis of neonatal jaundice. There are indications that other conjugation or detoxification mechanisms are also carried out in a different way from that of later life. The observation that after administration of sodium benzoate the excretion as hippuric acid is incomplete and delayed during the first three to four months of life (Vest, 1959) prompted us to investigate hippurate formation and acetylation in this age period.
The initial conditions for stellar protocluster formation. III The Herschel counterparts of the Spitzer Dark Cloud catalogue

Context. Galactic plane surveys of pristine molecular clouds are key for establishing a Galactic-scale view of star formation. For this reason, an unbiased sample of infrared dark clouds in the 10° < | l | < 65°, | b | < 1° region of the Galactic plane was built using Spitzer 8 μm extinction. However, intrinsic fluctuations in the mid-infrared background can be misinterpreted as foreground clouds. Aims. The main goal of this study is to disentangle real clouds in the Spitzer Dark Cloud (SDC) catalogue from artefacts due to fluctuations in the mid-infrared background. Methods. We constructed H2 column density maps at ~18″ resolution using the 160 μm and 250 μm data from the Herschel Galactic plane survey Hi-GAL. We also developed an automated detection scheme that confirms the existence of a SDC through its association with a peak on these Herschel column density maps. Detection simulations, along with visual inspection of a small sub-sample of SDCs, have been performed to get more insight into the limitations of our automated identification scheme. Results. Our analysis shows that 76( ± 19)% of the catalogued SDCs are real. This fraction drops to 55( ± 12)% for clouds with angular diameters larger than ~1 arcmin. The contamination of the PF09 catalogue by large spurious sources reflects the large uncertainties associated to the construction of the 8 μm background emission, a key stage in identiying SDCs. A comparison of the Herschel confirmed SDC sample with the BGPS and ATLASGAL samples shows that SDCs probe a unique range of cloud properties, reaching down to more compact and lower column density clouds than any of these two (sub-)millimetre Galactic plane surveys. Conclusions. Even though about half of the large SDCs are spurious sources, the vast majority of the catalogued SDCs do have a Herschel counterpart. The Herschel-confirmed sample of SDCs offers a unique opportunity to study the earliest stages of both low- and high-mass star formation across the Galaxy.
The a-subunit of the heterotrimeric G-protein affects jasmonate responses in Arabidopsis thaliana

Heterotrimeric G-proteins have been implicated in having a role in many plant signalling pathways. To understand further the role of G-proteins, a preliminary experiment was performed to assess the impact of the Ga subunit lossof-function mutation gpa1-1 on the Arabidopsis transcriptome. The analysis indicated that the Ga subunit may play a role in response to jasmonic acid (JA). Consistent with this, Ga mutants showed a reduced response to JA in inhibition of chlorophyll accumulation and root growth, whilst Ga gain-of-function plants overexpressing Ga showed the opposite phenotype. The levels of JA and related compounds were unaffected in the gpa1-1 mutant, as was autoregulation of the Allene Oxide Synthase (AOS) gene that encodes a key enzyme for JA biosynthesis. In contrast, further analyses using Ga lossand gain-of-function Arabidopsis lines indicated that Ga positively modulates the expression of the Vegetative Storage Protein (VSP) gene. This indicates that the Ga subunit regulates a subset of JAregulated genes defining a branch point in this signalling pathway in Arabidopsis. Further analysis of the impact of Ga loss of function upon the JA-regulated transcriptome using Arabidopsis full genome arrays indicated that up to 29% of genes that are >2-fold regulated by JA in the wild type are misregulated in the Ga mutant. This supports the observation that a significant proportion of, but not all, JA-regulated gene expression is mediated by Ga.
Correlative Electrophysiological and Anatomical Studies Concerning the Site of Origin of Escape Rhythm during Complete Atrioventricular Block in the Dog

Complete heart block was produced in eight dogs by the selective perfusion of physostdgmine or neostigmine into the atrioventricular (AV) node artery. A characteristic escape AV junctional rhythm emerged in each dog. After reversal of the cholinesterase paralysis with atropine, in each dog partial heart block was produced by an incision into the AV nodal region. In three of these eight dogs, a second incision placed slightly more anteriorly produced complete AV block which was followed by the emergence of an escape AV junctional rhythm similar to the one produced pharmacologically. Hearts of these three dogs were examined hiatologically with serial sections to determine the exact location of the incisions and their relationship to the AV node and His bundle. In each dog the incision that produced complete heart block passed directly through the junction of AV node with His bundle. In this region previous studies had demonstrated numerous P cells, which are thought to be the site of origin of normal cardiac automaticity. In each of the three hearts there were abundant P cells in continuity-with the His bundle distal to the cut producing heart block. Significance of these findings is discussed relative to the locus of action of acetylcholine within the AV junction, the site of origin of AV junctional rhythm, and some aspects of the experimental and therapeutic production of heart block. Ore Res 45:108-119, 1979
Comparisons of Mutants Lacking the Golgi UDP-Galactose or GDP-Mannose Transporters Establish that Phosphoglycans Are Important for Promastigote but Not Amastigote Virulence in Leishmania major

ABSTRACT Abundant surface Leishmania phosphoglycans (PGs) containing [Gal(β1,4)Man(α1-PO4)]-derived repeating units are important at several points in the infectious cycle of this protozoan parasite. PG synthesis requires transport of activated nucleotide-sugar precursors from the cytoplasm to the Golgi apparatus. Correspondingly, null mutants of the L. major GDP-mannose transporter LPG2 lack PGs and are severely compromised in macrophage survival and induction of acute pathology in susceptible mice, yet they are able to persist indefinitely and induce protective immunity. However, lpg2−L. mexicana amastigotes similarly lacking PGs but otherwise normal in known glycoconjugates remain able to induce acute pathology. To explore this further, we tested the infectivity of a new PG-null L. major mutant, which is inactivated in the two UDP-galactose transporter genes LPG5A and LPG5B. Surprisingly this mutant did not recapitulate the phenotype of L. major lpg2−, instead resembling the L. major lipophosphoglycan-deficient lpg1− mutant. Metacyclic lpg5A−/lpg5B− promastigotes showed strong defects in the initial steps of macrophage infection and survival. However, after a modest delay, the lpg5A−/lpg5B− mutant induced lesion pathology in infected mice, which thereafter progressed normally. Amastigotes recovered from these lesions were fully infective in mice and in macrophages despite the continued absence of PGs. This suggests that another LPG2-dependent metabolite is responsible for the L. major amastigote virulence defect, although further studies ruled out cytoplasmic mannans. These data thus resolve the distinct phenotypes seen among lpg2−Leishmania species by emphasizing the role of glycoconjugates other than PGs in amastigote virulence, while providing further support for the role of PGs in metacyclic promastigote virulence.
Physical basis of contact mechanics of surfaces

The conditions of contact interaction (pressure, displacement, temperature) of the surfaces of machine parts as the basis for their design and improvement are considered. It is noted that physics is the theoretical basis of the mechanics of interaction of surfaces. A structural hierarchy of interaction types is proposed. The place of mechanical interaction among known to science four types of interaction is defined: strong, weak, electromagnetic and gravitational. A hypothesis has been put forward and justified that in a given range of sizes, mechanical interaction can be considered the fifth interaction between the material objects of the world
Necrosis Is the Dominant Cell Death Pathway in Uropathogenic Escherichia coli Elicited Epididymo-Orchitis and Is Responsible for Damage of Rat Testis

Male infertility is a frequent medical condition, compromising approximately one in twenty men, with infections of the reproductive tract constituting a major etiological factor. Bacterial epididymo-orchitis results in acute inflammation most often caused by ascending canalicular infections from the urethra via the continuous male excurrent ductal system. Uropathogenic Escherichia coli (UPEC) represent a relevant pathogen in urogenital tract infections. To explore how bacteria can cause damage and cell loss and thus impair fertility, an in vivo epididymo-orchitis model was employed in rats by injecting UPEC strain CFT073 into the vas deference in close proximity to the epididymis. Seven days post infection bacteria were found predominantly in the testicular interstitial space. UPEC infection resulted in severe impairment of spermatogenesis by germ cell loss, damage of testicular somatic cells, a decrease in sperm numbers and a significant increase in TUNEL (+) cells. Activation of caspase-8 (extrinsic apoptotic pathway), caspase-3/−6 (intrinsic apoptotic pathway), caspase-1 (pyroptosis pathway) and the presence of 180 bp DNA fragments, all of which serve as indicators of the classical apoptotic pathway, were not observed in infected testis. Notably, electron microscopical examination revealed degenerative features of Sertoli cells (SC) in UPEC infected testis. Furthermore, the passive release of high mobility group protein B1 (HMGB1), as an indication of necrosis, was observed in vivo in infected testis. Thus, necrosis appears to be the dominant cell death pathway in UPEC infected testis. Substantial necrotic changes seen in Sertoli cells will contribute to impaired spermatogenesis by loss of function in supporting the dependent germ cells.
Regulation of a Novel Acidithiobacillus caldus Gene Cluster Involved in Metabolism of Reduced Inorganic Sulfur Compounds

ABSTRACT Acidithiobacillus caldus has been proposed to play a role in the oxidation of reduced inorganic sulfur compounds (RISCs) produced in industrial biomining of sulfidic minerals. Here, we describe the regulation of a new cluster containing the gene encoding tetrathionate hydrolase (tetH), a key enzyme in the RISC metabolism of this bacterium. The cluster contains five cotranscribed genes, ISac1, rsrR, rsrS, tetH, and doxD, coding for a transposase, a two-component response regulator (RsrR and RsrS), tetrathionate hydrolase, and DoxD, respectively. As shown by quantitative PCR, rsrR, tetH, and doxD are upregulated to different degrees in the presence of tetrathionate. Western blot analysis also indicates upregulation of TetH in the presence of tetrathionate, thiosulfate, and pyrite. The tetH cluster is predicted to have two promoters, both of which are functional in Escherichia coli and one of which was mapped by primer extension. A pyrrolo-quinoline quinone binding domain in TetH was predicted by bioinformatic analysis, and the presence of an o-quinone moiety was experimentally verified, suggesting a mechanism for tetrathionate oxidation.
CD150-mediated Akt signalling pathway in normal and malignant B cells.

AIM To study upstream and downstream events in CD150-mediated Akt signaling pathway in normal human B cells, EBV-transformed lymphoblastoid (LCL) and malignant Hodgkin's lymphoma (HL) B cell lines. METHODS To access protein-protein interaction we applied immunoprecipitation, Western blot analysis and surface plasmon resonance (SPR) technique. A novel modification of SPR technique using reduced glutathione bound to golden surface was proposed. Immunostaining and isolation of cytoplasmic fractions and nuclear extracts were performed to detect proteins' localization in cells. Western blot analysis was performed to follow up the phosphorylation of proteins on specific sites and proteins' expression level. RESULTS It was shown that CD150 ligation induced Akt activation in normal tonsillar B cells (TBC), SH2D1A positive LCL and HL B cell lines. The p85α subunit of PI3K co-precipitated with CD150 cytoplasmic tail. This direct association depends on tyrosine phosphorylation and is mediated by N terminal SH2 domain of p85α. CD150 initiated phosphorylation of FoxO1 transcription factor in normal B cells as well as in LCL MP-1 and HL cell line L1236. At the same time, CD150 ligation triggered GSK-3β kinase phosphorylation only in immortalized LCL MP-1 and HL cell line L1236. CONCLUSIONS We have demonstrated that CD150 receptor could trigger PI3K-mediated Akt signaling pathway in normal, EBV-transformed and malignant B cells. CD150-mediated phosphorylation of Akt downstream targets GSK-3β and FoxO1 in EBV-transformed and HL cells could be one of the mechanisms to avoid apoptosis and support survival program in these immortalized B cells.
Interferon-γ selectively increases epithelial permeability to large molecules by activating different populations of paracellular pores

Impairment of the gut epithelial barrier by agents such as IFNγ may play a key role in the pathogenesis of inflammatory disorders by increasing the paracellular penetration of luminal macromolecules, potentially including bacterial antigens. Owing to limitations of current paracellular probes, little is known about the precise functional changes induced by IFNγ and how these relate to the development of increased macromolecular permeability. Here we investigate how IFNγ modulates this pathway in T84 monolayers using a novel profiling technique that resolves different populations of paracellular pores by simultaneous analysis of 24 permeability probes of defined molecular size. Two types of functional pore present in control monolayers, an abundant restrictive pore with a radius of ∼4.5 Å and a much larger but infrequent, non-restrictive pore, were differentially regulated by IFNγ. Incubation with IFNγ dose-dependently and reversibly increased the frequency of the non-restrictive pores while having no significant effect on the restrictive component. Cytokine-induced increases in β, the descriptor of the non-restrictive pore, correlated closely with increased permeability to large molecules (10 kDa) including E. coli-derived lipopolysaccharide, but not small (0.182 kDa) molecules. This effect was associated with changes in expression of the tight junction proteins occludin and claudin-1. These data suggest that IFNγ selectively increases the transepithelial flux of large molecules by activating specific pathways within the junctional pore. One hypothesis is that this process may be activated in the early stages of the inflammatory response, facilitating the passage of large and potentially antigenic molecules across the gut without gross disruption of the barrier to small molecules.
Violence and Other Bases of Power in Marriage.

AUTHOR Frieze, Irene Hanson; McHugh, Maureen C. TITLE Violence and Other Bases of Power in Marriage. SPONS AGENCY National Inst. of Mental Health (DHHS), Rockville, Md. National Center for the Control and Prevention of Rape. PUB DATE Aug 81 GRANT NIMH-R01-MH-30193 NOTE 48p. ; Paper presented at the Annual Convention of the American Psychological Association (89th, Los Angeles, CA, August 24-26, 1981). PUB TYPE Reports Research/Technical (143) -Speeches/Conference Papers (150)
Developing Learning System Continuance with Teachers and Students: Case Study of the Echo360 Lecture Capturing System

Research on learning system continuance has been focused mostly on students’ conscious behaviour. While the institutional decision to adopt and sustain the deployment of a new technology provides strong support for organisational adoption, the key factor for achieving long-term continuance relies on individual behaviour from different stakeholders, e.g., students, support staff and teachers. Existing literature on Information Systems (IS) continuance, however, suffers from weaknesses. On the one hand, perceptions from other stakeholders, such as teachers and support staff, are often neglected in the literature. On the other hand, there is a theoretical gap in explaining continuance behaviour through traditional models because unconscious automatic behaviour (e.g., IS habit) plays a more critical role in influencing continuance behaviour than previously expected. This study takes a qualitative approach to identify perceptions from students and teachers on which features and usage patterns of a lecture capturing system (Echo360) would develop long-term continuance behaviour through both conscious and unconscious behaviours. Our results suggest that long-term continuance can be achieved by a combination of Information Technology (IT) artefact extension (e.g., providing better search functionality and multimedia tagging) and developed IS habits through curriculum design.