Miracle-dz/UniFAR-FTUs huggingface dataset:
Mixed Lineage Leukemia 5 (MLL5) Protein Regulates Cell Cycle Progression and E2F1-responsive Gene Expression via Association with Host Cell Factor-1 (HCF-1)*

Background: MLL5 protein regulates cell cycle progression. Results: MLL5 regulates the expression of E2F1-target genes through an association with HCF-1. Conclusion: MLL5 stimulates H3K4 trimethylation at E2F1 responsive promoters and cause transcriptional activation of E2F1 target genes to facilitate the G1 to S phase transition. Significance: Our results reveal a novel molecular mechanism of MLL5 protein in the regulation of cell cycle progression. Trithorax group proteins methylate lysine 4 of histone 3 (H3K4) at active gene promoters. MLL5 protein, a member of the Trithorax protein family, has been implicated in the control of the cell cycle progression; however, the underlying molecular mechanism(s) have not been fully determined. In this study, we found that the MLL5 protein can associate with the cell cycle regulator “host cell factor” (HCF-1). The interaction between MLL5 and HCF-1 is mediated by the “HCF-1 binding motif” (HBM) of the MLL5 protein and the Kelch domain of the HCF-1 protein. Confocal microscopy showed that the MLL5 protein largely colocalized with HCF-1 in the nucleus. Knockdown of MLL5 resulted in reduced cell proliferation and cell cycle arrest in the G1 phase. Moreover, down-regulation of E2F1 target gene expression and decreased H3K4me3 levels at E2F1-responsive promoters were observed in MLL5 knockdown cells. Additionally, the core subunits, including ASH2L, RBBP5, and WDR5, that are necessary for effective H3K4 methyltransferase activities of the Trithorax protein complexes, were absent in the MLL5 complex, suggesting that a distinct mechanism may be used by MLL5 for exerting its H3K4 methyltransferase activity. Together, our findings demonstrate that MLL5 could associate with HCF-1 and then be recruited to E2F1-responsive promoters to stimulate H3K4 trimethylation and transcriptional activation, thereby facilitating the cell cycle G1 to S phase transition.
Friends or Foes? How Managerial Perceptions of the Political Opportunity Structure Shape Nonprofit Advocacy

Abstract Policy advocacy is an important tool that nonprofit managers use to build relationships with public officials and others in furtherance of their charitable missions. Through advocacy, nonprofits work to promote policies affecting their constituencies, maintain public funding, or strengthen the nonprofit sector as a whole. Scholarship on nonprofit advocacy often considers the organizational or resource environment, however, insufficient attention has focused on the policy environment as a factor shaping nonprofit advocacy. This article draws on the concept of political opportunity structure from the sociological study of social movements to understand nonprofit policy advocacy. The political opportunity framework focuses on how aspects of the political environment influence political action. Using data from a recent statewide survey of Massachusetts nonprofit organizations (n = 656, 55% response rate), we find evidence of a nonlinear relationship between managers’ perceptions of the political opportunity structure and the likelihood that a nonprofit engages in policy advocacy.
POLLINATION SYSTEMS AS ISOLATING MECHANISMS IN ANGIOSPERMS

82 The opinion, once held rather widely by biologists, that related species are generally, if not universally, separated by barriers to reproduction involving incompatibility and hybrid sterility has undergone some qualifications in recent years. The modification of the time-honored view has been in part a consequence of the discovery that species of higher plants, which occupy the same range in nature without evident hybridization, may nevertheless yield fertile progeny when crossed in the breeding plot (Anderson, 1948). Two sets of processes are now known whereby intercompatible and interfertile species of flowering plants can occur sympatrically and still maintain their distinctness. The first of these is the non-establishment of the hybrid seedlings, due to the lack of an available ecological niche; the second is the non-production of hybrids, due to the failure of interspecific pollination. The, effect of ecological factors on the isolation of interfertile, sympatric species has been dealt with in several recent publications (Epling, 1947a, 1947b; Stebbins, Matzke, and Epling, 1947; Anderson, op, cit.). The purpose of the present paper is to investigate the occurrence and distribution in angiosperms of isolating mechanisms operating at the critical stage of pollination.
Charge recombination reactions in photosystem II. 2. Transient absorbance difference spectra and their temperature dependence.

Absorbance difference spectra of the transient states in photosystem II (PS II) have been examined in the Qv absorption region between 660 and 700 nm. The P680+Pheo-/P680Pheo, 3P680/P680, and P680+QA-/P680QA spectra were measured in O2-evolving PS II core complexes from Synechococcus and PS II-enriched membrane fragments from spinach. The low-temperature absorbance difference spectra vary only slightly between both PS II preparations. The 3P680/P680 spectrum is characterized by a bleaching at 685 nm at 25 K and indicates weak exciton coupling with neighboring pigment(s). We conclude that P680 absorbs at 685 nm in more intact PS II preparations at cryogenic temperature. The difference spectra of the radical pairs are strongly temperature dependent. At low temperature the P680+QA-/P680QA- spectrum exhibits the strongest bleaching at 675 nm whereas the P680+Phe-/P680Pheo spectra show two distinct bleaching bands at 674 and 684 nm. It is suggested that an electrochronic red shift resulting in a bleaching at 675 nm and an absorbance increase at about 682 nm dominates the spectral features of the charge-separated states. On the basis of the present results and those in the literature, we conclude that the interactions between the pigments and especially the organization of the primary donor must be quite different in PS II compared to bacterial reaction centers, although the basic structural arrangement of the pigments might be similar. Spectral data obtained with samples in the presence of singly and doubly reduced QA indicate that the primary photochemistry in PS II is not strongly influenced by the redox state of QA at low temperature and confirm the results of the accompanying paper [Van Mieghem, F. J. E. , Brettel, K. , Hillmann, B. , Kamlowski, A. , Rutherford, A. W. , & Schlodder, E. (1995) Biochemistry 34, 4798-4813]. The spectra of the primary radical pair and the reaction center triplet obtained with more intact PS II preparations differ widely from those of D1/D2/cyt b-559 complexes. In the latter sample, where 3P680 formation results in a bleaching at 680 nm, the P680+Pheo-/P680Pheo spectrum shows only one broad bleaching band at about 680 nm, and the main bleaching due to photoaccumulation of Pheo- at 77 K appears at 682 nm instead of 685 nm in PS II core complexes. This indicates that the removal of the core antenna which is accompanied by the loss of QA causes also structural changes of the reaction center.
Induction of ephrin‐B1 and EphB receptors during denervation‐induced plasticity in the adult mouse hippocampus

It has been widely demonstrated that Eph receptors and their ephrin ligands play multiple pivotal roles in the development of the nervous system. However, less is known about their roles in the adult brain. Here we reported the expression of ephrin‐B1 and its cognate EphB receptors in the adult mouse hippocampus at 3, 7, 15, 30 and 60 days after transections of the entorhinal afferents. In situ hybridization and immunohistochemistry showed the time‐dependent up‐regulation of ephrin‐B1 in the denervated areas of the hippocampus, which initiated at 3 days postlesion (dpl), reached maximal levels at 7–15 dpl, remained slightly elevated at 30 dpl and recovered to normal levels by 60 dpl. Double labeling of ephrin‐B1 and glial fibrillary acidic protein revealed that ephrin‐B1‐expressing cells in the denervated areas were reactive astrocytes. Furthermore, a ligand‐binding assay using ephrin‐B1/Fc chimera protein also displayed the up‐regulation of EphB receptors in the denervated areas of the hippocampus in a similar manner to that of ephrin‐B1. Within the first week postlesion, the EphB receptors were expressed by reactive astrocytes. After 7 dpl, however, EphB receptors were expressed not only by reactive astrocytes but also first by sprouting axons and later by regrowing dendrites. These results suggest that the ephrin‐B1/EphB system may participate in the lesion‐induced plasticity processes in the adult mouse hippocampus.
Correlation between Increased Susceptibility to Primary Toxoplasma gondii Infection and Depressed Production of Gamma Interferon in Pregnant Mice

To explore a possible mechanism of pregnancy‐associated suppression of T cell‐mediated immunity to Toxoplasma gondii, acquired resistance and gamma interferone (IFN‐γ) production in pregnant mice were compared with those in virgin mice after infection with the S‐273 strain of this protozoan parasite. The 50% lethal dose of this strain was less than 200 tachyzoites for pregnant mice and 2,800 organisms for virgin controls. Toxoplasma‐induced production of both IFN‐α and IFN‐γ in the bloodstream of pregnant mice was significantly depressed as compared with that in virgin controls. The administration of recombinant murine IFN‐γ (rMuIFN‐γ) resulted in a significant decrease of mortality and parasitic growth in the organs of pregnant mice infected with a lethal dose of S‐273 strain tachyzoites. Thus, the impairment of T cell‐mediated immune responses was evident in pregnant mice from the impaired IFN‐γ‐generating capacity and poor survival rate after primary infection with Toxoplasma. When mice with chronic Toxoplasma infection were injected with specific antigen, the resultant production of IFN‐γ was also significantly suppressed during pregnancy. However, there was no direct correlation between the serum levels of IFN‐γ and susceptibility to reinfection, since the mortality rate of chronically infected pregnant mice after the challenge with the high virulent RH strain was not significantly higher than that of virgin controls.
Llama single‐domain antibodies directed against nonconventional epitopes of tumor‐associated carcinoembryonic antigen absent from nonspecific cross‐reacting antigen

Single‐domain antibodies (sdAbs), which occur naturally in camelids, are endowed with many characteristics that make them attractive candidates as building blocks to create new antibody‐related therapeutic molecules. In this study, we isolated from an immunized llama several high‐affinity sdAbs directed against human carcinoembryonic antigen (CEA), a heavily glycosylated tumor‐associated molecule expressed in a variety of cancers. These llama sdAbs bind a different epitope from those defined by current murine mAbs, as shown by binding competition experiments using immunofluorescence and surface plasmon resonance. Flow cytometry analysis shows that they bind strongly to CEA‐positive tumor cells but show no cross‐reaction toward nonspecific cross‐reacting antigen, a highly CEA‐related molecule expressed on human granulocytes. When injected into mice xenografted with a human CEA‐positive tumor, up to 2% of the injected dose of one of these sdAbs was found in the tumor, despite rapid clearance of this 15 kDa protein, demonstrating its high potential as a targeting moiety. The single‐domain nature of these new anti‐CEA IgG fragments should facilitate the design of new molecules for immunotherapy or diagnosis of CEA‐positive tumors.
Engagement of the Cellular Receptor for Glycoprotein B of Human Cytomegalovirus Activates the Interferon-Responsive Pathway

ABSTRACT Cells respond to contact with human cytomegalovirus (HCMV) virions by initiating intracellular signaling and gene expression characteristic of the interferon (IFN)-responsive pathway. Herein, we demonstrate that a principal mechanism of HCMV-induced signal transduction is via an interaction of the primary viral ligand, glycoprotein B (gB), with its cellular receptor. Cells incubated with a purified, soluble form of gB resulted in the transcriptional upregulation of IFN-responsive genes OAS and ISG54 (encoding 2′-5′ oligoadenylate synthetase and an IFN-stimulated gene product of 54 kDa) to a comparable level as virions or IFN. Gene induction was an immediate and direct response to gB which did not require de novo protein synthesis. Neither the initial virus attachment site, heparan sulfate proteoglycans, nor the IFN-α/β or IFN-γ receptors are involved in the response. Pleotropic protein phosphorylation was required for cellular gene induction, and the mitogen-activated protein kinases ERK1 and ERK2 were activated in response to the ligand. Together these data indicate that a principal means by which cytomegalovirus induces intracellular signaling and activation of the interferon-responsive pathway is via an interaction of gB with an as yet unidentified, likely novel cellular receptor that interfaces with the IFN signaling pathway.
Ascidian Sperm Glycosylphosphatidylinositol-anchored CRISP-like Protein as a Binding Partner for an Allorecognizable Sperm Receptor on the Vitelline Coat*

Although ascidians are hermaphroditic, many species including Halocynthia roretzi are self-sterile. We previously reported that a vitelline coat polymorphic protein HrVC70, consisting of 12 EGF (epidermal growth factor)-like repeats, is a candidate allorecognition protein in H. roretzi, because the isolated HrVC70 shows higher affinity to nonself-sperm than to self-sperm. Here, we show that a sperm 35-kDa glycosylphosphatidylinositol-anchored CRISP (cysteine-rich secretory protein)-like protein HrUrabin in a low density detergent-insoluble membrane fraction is a physiological binding partner for HrVC70. We found that HrVC70 specifically interacts with HrUrabin, which had been separated by SDS-PAGE and transferred onto a nitrocellulose membrane. HrUrabin has an N-linked sugar chain, essential for binding to HrVC70. HrUrabin mRNA is expressed in the testis but not in the ovary, and the protein appears to be localized on the surface of sperm head and tail. Anti-HrUrabin antibody, which neutralizes the interaction between HrUrabin and HrVC70, potently inhibited fertilization and allorecognizable sperm-binding to HrVC70-agarose. However, no significant difference in the binding ability of HrUrabin to HrVC70 was observed in autologous and allogeneic combinations by Far Western analyses. These results indicate that sperm-egg binding in H. roretzi is mediated by the molecular interaction between HrUrabin on the sperm surface and HrVC70 on the vitelline coat, but that HrUrabin per se is unlikely to be a direct allorecognition protein.
Predictors of deterioration of lung function in cystic fibrosis *

The severity of lung disease in cystic fibrosis (CF) may be related to the type of mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and to environmental and immunological factors. Since pulmonary disease is the main determinant of morbidity and mortality in CF, it is important to identify factors that can explain and predict this variation. The aim of this longitudinal study of the whole Swedish CF population over age 7 years was to correlate genetic and clinical data with the rate of decline in pulmonary function. The statistical analysis was performed using the mixed model regression method, supplemented with calculation of relative risks for severe lung disease in age cohorts.
Laparoscopic ovariectomy in dogs: comparison between single portal and two-portal access.

OBJECTIVE To compare surgical times and perioperative complication rates of single portal access and 2-portal laparoscopic ovariectomy (LapOVE) in dogs using a bipolar vessel sealer/divider device, and to evaluate the performance of novice laparoscopists for right ovariectomy. STUDY DESIGN Controlled clinical trial. ANIMALS Female dogs (n=42). METHODS Dogs were divided into groups: 1=single portal and 2=2 portal. LapOVE was performed using a 5 mm vessel sealer/divider device and a 10 mm operating laparoscope (Group 1) or a 5 mm laparoscope (Group 2). Dog characteristics (weight, body condition score, ovarian ligament fat score), operative time, and perioperative complication rate were compared between groups. Right ovariectomy duration was evaluated for 2 novice laparoscopists. RESULTS No significant difference was found in mean total surgical time between group 1 (21.07 min/s) and group 2 (19.06 min/s). Factors significantly affecting times included body condition scores, ovarian ligament fat score, ovarian bleeding, and surgeon expertise. Minor complications (bleeding from ovaries or after splenic trauma) occurred and were similar in both groups. Bleeding was correlated to body condition score and ovarian ligament fat score. Interindividual differences were found among surgeons for right ovariectomy time. CONCLUSIONS Single portal access LapOVE using vessel sealer/divider device is feasible, safe, and does not significantly increase total surgical time in comparison with 2-portal approach. Laparoscopic skills may play a role in ability to perform single portal LapOVE. CLINICAL RELEVANCE LapOVE can be performed using single portal access.
Early haemorrhagic morbidity and mortality during remission induction with or without all‐trans retinoic acid in acute promyelocytic leukaemia

A total of 622 consecutive patients with acute promyelocytic leukaemia (APL) treated within the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) group during 1989–97 have been reviewed to assess the clinical effectiveness of all‐trans retinoic acid (ATRA) on the incidence of early haemorrhagic deaths and on APL‐associated coagulopathy. Of them, 499 were treated with idarubicin plus ATRA (study A) and 123 with Idarubicin alone (study B). In both studies, similar guidelines for supportive treatment were used. Haemorrhagic symptoms were evaluated according to a reproducible score system. Deaths occurring within 10 d of starting treatment were 19 (3.8%) in study A and nine (7.3%) in study B (P = 0.09), with 15 (3%) and five (4.1%) (P not significant) due to haemorrhage. Overall, induction mortality was 7.6% and 16.2% respectively (P < 0.003). In study A, days with platelet counts ≤ 20 × 109/l or with fibrinogen ≤ 1 g/L were reduced by about 30%, the haemorrhagic score by 50% and the consumption of blood products by about 40%, and fewer patients were treated with antihaemorrhagic drugs (39% vs. 61%; P < 0.001). On multivariate analysis, early deaths were influenced by blast count at diagnosis > 30 × 109/l (P < 0.001) in both studies, and by a haemorrhagic score of 3 in study A (P < 0.001).
Job Safety and Contract Workers in the Petrochemical Industry

The legal rules for assigning liability for the costs of accidents penalize petrochemical plants that exercise direct control over contract employees. Evidence from diverse sources indicates that these liability rules lead plant management to give primary responsibility for the safety training and supervision of contract employees to contractors. However, analysis of the determinants of accidents suggests that host plants offer more effective safety training and supervision than do contractors. It follows that accident rates in the petrochemical industry would be reduced if liability rules were altered so that host plants had greater incentives to take primary responsibility for the safety training and supervision of contract workers.
Dishevelled interacts with the DIX domain polymerization interface of Axin to interfere with its function in down-regulating β-catenin

Wnt/β-catenin signaling controls numerous steps in normal animal development and can also cause cancer if inappropriately activated. In the absence of Wnt, β-catenin is targeted continuously for proteasomal degradation by the Axin destruction complex, whose activity is blocked upon Wnt stimulation by Dishevelled, which recruits Axin to the plasma membrane and assembles it into a signalosome. This key event during Wnt signal transduction depends on dynamic head-to-tail polymerization by the DIX domain of Dishevelled. Here, we use rescue assays in Drosophila tissues and functional assays in human cells to show that polymerization-blocking mutations in the DIX domain of Axin disable its effector function in down-regulating Armadillo/β-catenin and its response to Dishevelled during Wnt signaling. Intriguingly, NMR spectroscopy revealed that the purified DIX domains of the two proteins interact with each other directly through their polymerization interfaces, whereby the same residues mediate both homo- and heterotypic interactions. This result implies that Dishevelled has the potential to act as a “natural” dominant-negative, binding to the polymerization interface of Axin's DIX domain to interfere with its self-assembly, thereby blocking its effector function.
The Acquisition of Contrastive andNon-contrastive Anaphoric Forms in Brazilian Portuguese

In this article I discuss the main syntactic, semantic and pragmatic characteristics of the Brazilian Portuguese (BP) proform ele (he/him) and the intensified proform ele mesmo (him-self). Contrary to what is commonly assumed in the Brazilian literature, I will argue that the proform ele is not a pronoun and is not regulated by Principle B of Binding Theory. Also, I will argue that the intensified proform ele mesmo is not subject to Principle A of the Binding Theory. These observations will then be taken into consideration in order to discuss their acquisition. I will present the results of a study conducted with children acquiring BP as their mother tongue, showing that the anaphor se and the nonemphatic form ele are acquired before the emphatic ele mesmo. The paper is organized as follows. In section 2, I compare the emphatic ele mesmo to the reflexive se and to the non-emphatic proform ele. Syntactic, semantic and pragmatic aspects are discussed. In section 3, acquisition data from other languages are discussed. Section 4 discusses the acquisition data from BP. Section 5 is the conclusion.
Revealing the Photophysics of Gold-Nanobeacons via Time-Resolved Fluorescence Spectroscopy

1Department of Physics, Beihang University, Beijing 100191, China 2Photophysics Group, Department of Physics, SUPA, University of Strathclyde, 107 Rottenrow, Glasgow G4 0NG, UK 3Department of Chemical and Process Engineering, University of Strathclyde, 75 Montrose Street, Glasgow G1 1XJ, UK 4Strathclyde Institute of Pharmacy and Biomedical Sciences, 204 George Street, Glasgow G1 1XW, UK *Corresponding author: y.chen@strath.ac. uk