Miracle-dz/UniFAR-FTUs huggingface dataset:
G-Protein β Subunit of Cochliobolus heterostrophus Involved in Virulence, Asexual and Sexual Reproductive Ability, and Morphogenesis

ABSTRACT Previous work established that mutations in mitogen-activated protein (MAP) kinase (CHK1) and heterotrimeric G-protein α (Gα) subunit (CGA1) genes affect the development of several stages of the life cycle of the maize pathogen Cochliobolus heterostrophus. The effects of mutating a third signal transduction pathway gene, CGB1, encoding the Gβ subunit, are reported here. CGB1 is the sole Gβ subunit-encoding gene in the genome of this organism. cgb1 mutants are nearly wild type in vegetative growth rate; however, Cgb1 is required for appressorium formation, female fertility, conidiation, regulation of hyphal pigmentation, and wild-type virulence on maize. Young hyphae of cgb1 mutants grow in a straight path, in contrast to those of the wild type, which grow in a wavy pattern. Some of the phenotypes conferred by mutations in CGA1 are found in cgb1 mutants, suggesting that Cgb1 functions in a heterotrimeric G protein; however, there are also differences. In contrast to the deletion of CGA1, the loss of CGB1 is not lethal for ascospores, evidence that there is a Gβ subunit-independent signaling role for Cga1 in mating. Furthermore, not all of the phenotypes conferred by mutations in the MAP kinase CHK1 gene are found in cgb1 mutants, implying that the Gβ heterodimer is not the only conduit for signals to the MAP kinase CHK1 module. The additional phenotypes of cgb1 mutants, including severe loss of virulence on maize and of the ability to produce conidia, are consistent with CGB1 being unique in the genome. Fluorescent DNA staining showed that there is often nuclear degradation in mature hyphae of cgb1 mutants, while comparable wild-type cells have intact nuclei. These data may be genetic evidence for a novel cell death-related function of the Gβ subunit in filamentous fungi.
Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors.

BACKGROUND Adenoid cystic carcinoma (ACC) is a subtype of malignant salivary gland tumors (MSGT), in which 90% of cases express cKIT. Dasatinib is a potent and selective inhibitor of five oncogenic protein tyrosine kinases (PTKs)/kinase families including cKIT. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT. PATIENTS AND METHODS In a two-stage design, patients with progressive, recurrent/metastatic ACC (+cKIT) and non-ACC MSGT (separate cohort) were treated with dasatinib 70 mg p.o. b.i. d. Response was assessed every 8 weeks using RECIST. RESULTS Of 54 patients: 40 ACC, 14 non-ACC (1, ineligible excluded); M:F = 28 : 26, median age 56 years (range 20-82 years), ECOG performance status 0 : 1 : 2 = 24 : 28 : 2, prior radiation: 44, prior chemotherapy: 21. The most frequent adverse events (AEs) (as % of patients, worst grade 2 or higher) were: fatigue (28%), nausea (19%), headache (15%), lymphopenia (7%), dyspnea (11%), alanine aminotransferase increased (7%), anorexia (7%), vomiting (7%), alkaline phosphatase increased (6%), diarrhea (6%), neutropenia (6%), and noncardiac chest pain (6%). No grade 4 AE occurred, 15 patients experienced a grade 3 AE, primarily dyspnea (5) and fatigue (4), and cardiac toxicity (1 prolonged QTc). Among ACC patients, best response to dasatinib: 1 patient (2.5%) had partial response, 20 patients (50%) had stable disease (SD) (3-14 months), 12 patients (30%) had PD, 2 withdrew, 3 discontinued therapy due to AE, and 2 died before cycle 2. Median progression-free survival was 4.8 months. Median overall survival was 14.5 months. For 14 assessable non-ACC patients, none had objective response, triggering early stopping rule. Seven had SD (range 1-7 months), 4 PD, 2 discontinued therapy due to AE, and 1 died before cycle 2. CONCLUSION Although there was only one objective response, dasatinib is well tolerated, with tumor stabilization achieved by 50% of ACC patients. Dasatinib demonstrated no activity in non-ACC MSGT.
Asymmetric dimethylarginine and arterial stiffness in patients with rheumatoid arthritis: A case–control study

Objective To investigate whether levels of asymmetric dimethylarginine (ADMA), as a measure of endothelial dysfunction, are higher in patients with rheumatoid arthritis compared with healthy control subjects. The relationships between ADMA and surrogate measures of arterial stiffness were evaluated. Methods Patients with rheumatoid arthritis and healthy control subjects were recruited. ADMA was quantified via enzyme-linked immunosorbent assay. Arterial stiffness was evaluated using pulse wave analysis. Results There was no significant difference in plasma ADMA concentration between patients with rheumatoid arthritis (n = 30) and healthy controls (n = 30). Aortic augmentation pressure was significantly higher in patients than in controls. C-reactive protein and Health Assessment Questionnaire score were independent predictors of arterial stiffness in patients. There was no relationship between ADMA concentration and aortic augmentation pressure in the study population as a whole. Conclusions Arterial stiffness appears to be increased in rheumatoid arthritis and independently associated with systemic inflammation and physical disability. ADMA concentration was not increased in this small group of patients with rheumatoid arthritis compared with healthy controls; nor was it associated with arterial stiffness.
A Flexible Capacitive Pressure Sensor for Wearable Respiration Monitoring System

This paper presents the design, fabrication, and characterization of a wearable capacitive pressure sensor for respiration-monitoring systems. For the dielectric layer of the proposed capacitive sensor, Porous Ecoflex with a porosity of ~36% was prepared from a manually made sugar cube via a simple melting process. A polydimethylsiloxane-based silver nanowire and carbon fibers thin films were used for the sensor electrodes. The fabricated flexible pressure sensor exhibited a high sensitivity of 0.161 kPa−1 for low pressure regime (<10 kPa), a wide working pressure range of <200 kPa, and a high durability over 6000 cycles. Since the proposed sensor is flexible and resizable, it can be integrated into clothes and easily placed at any location of the human body. Finally, the practicality of the sensor was successfully demonstrated by integrating the sensor into a waist belt to monitor the real-time respiration signal of the human being. The finding is highly useful to monitor respiration signal for the detection of diseases, such as sleep apnea, asthma, and others.
Post‐translational synaptic protein modification as substrate for long‐lasting, remote memory: An initial test

The current view of the molecular basis for information storage is that post‐translational modification (PTM) of brain proteins is important for the early stages of memory storage and that protein synthesis is necessary for long‐lasting memory. This view has been challenged by the proposal that PTM of synaptic proteins is the critical instructive mechanism underlying both recent as well as long‐lasting memories (Routtenberg and Rekart, 2005 ). As an initial test, a broad spectrum serine/threonine kinase inhibitor (H‐7) was delivered bilaterally to rat anterior cingulate cortex 1 h before a 3 week retention test of contextual fear conditioning. This significantly blocked 21‐Day retention. In the second experiment evaluating extinction of a 21‐Day remote memory, H‐7 injected into mouse medial prefrontal cortex blocked fear extinction. As the H‐7‐induced impairment in 21‐Day retention was indexed by a decrease in freezing, while the extinction blockade by no decrease in freezing, the results could not be ascribed to a direct effect of the drug on behavioral performance. This represents the first demonstration, to our knowledge, that PTM inhibition, here serine/threonine kinase activity, interferes with long‐lasting memory, providing initial support for the PTM model. © 2006 Wiley‐Liss, Inc.
Cell to Cell Signalling via Exosomes Through esRNA

Exosomes are small vesicles of endosomal origin that can be released by many different cells to the microenvironment. Exosomes have been shown to participate in the immune system, by mediating antigen presentation. We have recently shown the presence of both mRNA and microRNA in exosomes, specifically in exosomes derived from mast cells. This RNA can be transferred between one mast cell to another, most likely through fusion of the exosome to the recipient cell membrane. The delivered RNA is functional, as the mRNA can lead to translation of new proteins in a recipient cell. The RNA shuttled between cells via exosomes is called esRNA. We propose that several types of exosomes may exist, and that an additional function of exosomes is to communicate to neighboring cells through delivery of RNA-signals.
Aortocaval Compression in Pregnancy: The Effect of Changing the Degree and Direction of Lateral Tilt on Maternal Cardiac Output

IMPLICATIONS Using thoracic bioimpedance to measure maternal cardiac output, we were unable to demonstrate any benefit from increasing the magnitude of lateral table tilt. This implies that it is unnecessary to use extremes of lateral table tilt in healthy pregnancy although this may not apply to women with cardiac compromise or regional anesthesia.
Dissecting Amyloid Beta Deposition Using Distinct Strains of the Neurotropic Parasite Toxoplasma gondii as a Novel Tool

Genetic and pathologic data suggest that amyloid beta (Aβ), produced by processing of the amyloid precursor protein, is a major initiator of Alzheimer’s disease (AD). To gain new insights into Aβ modulation, we sought to harness the power of the coevolution between the neurotropic parasite Toxoplasma gondii and the mammalian brain. Two prior studies attributed Toxoplasma-associated protection against Aβ to increases in anti-inflammatory cytokines (TGF-β and IL-10) and infiltrating phagocytic monocytes. These studies only used one Toxoplasma strain making it difficult to determine if the noted changes were associated with Aβ protection or simply infection. To address this limitation, we infected a third human amyloid precursor protein AD mouse model (J20) with each of the genetically distinct, canonical strains of Toxoplasma (Type I, Type II, or Type III). We then evaluated the central nervous system (CNS) for Aβ deposition, immune cell responses, global cytokine environment, and parasite burden. We found that only Type II infection was protective against Aβ deposition despite both Type II and Type III strains establishing a chronic CNS infection and inflammatory response. Compared with uninfected and Type I-infected mice, both Type II- and Type III-infected mice showed increased numbers of CNS T cells and microglia and elevated pro-inflammatory cytokines, but neither group showed a >2-fold elevation of TGF-β or IL-10. These data suggest that we can now use our identification of protective (Type II) and nonprotective (Type III) Toxoplasma strains to determine what parasite and host factors are linked to decreased Aβ burden rather than simply with infection.
Estimating risk of breast cancer in carriers of BRCA1 and BRCA2 mutations: a meta‐analytic approach

Estimates of penetrance (or risk) of breast cancer among BRCA mutation carriers in published studies are heterogeneous, prohibiting direct combined estimates. Estimates of prevalence of BRCA mutations are more homogeneous and could allow combined estimates of prevalence. We propose a combined estimator of penetrance from combined estimates of the prevalence of BRCA mutations in women with and without breast cancer and from the probability of breast cancer by using Bayes' Theorem. The relative risk of having breast cancer with positive family history and the prevalence of positive family history contribute to the combined estimate of penetrance if family history is present. The combined estimate incorporates variation in estimates from different resources. The method is illustrated by using data from Ashkenazi Jewish women unselected for family history and for those with family history. Risks of breast cancer conferred by BRCA1 and BRCA2 mutations are estimated to be 8.39 per cent (6.56, 10.68 per cent) and 2.66 per cent (1.85, 3.82 per cent) by 40 years old, and 47.45 per cent (37.39, 57.72 per cent) and 31.85 per cent (23.72, 41.26 per cent) by 75 years old, respectively. For those with family history, risks of breast cancer conferred by BRCA mutations appear to be higher. Copyright © 2007 John Wiley & Sons, Ltd.
Association of β-defensin gene copy number variations with ankylosing spondylitis in Chinese population: A case–control study

Objectives. To explore the association of β-defensin gene copy number variations (CNVs) with ankylosing spondylitis (AS). Methods. In this study, 405 unrelated Chinese Han patients with AS and 401 unrelated healthy controls were enrolled. The copy numbers of DEFB4 gene (2 fragments) were measured by AccuCopy™ methods. The association of DEFB4 gene CNVs with AS susceptibility was analyzed by chi-square and logistic regression models. Besides, P values, odds ratio, and 95% confidence intervals (CIs) were used to estimate the effects of risk. Results. The range of DEFB4_1 CN was 0–7 and the range of DEFB4_2 CN was 1–8 both in patients and controls. P values of χ2 trend test for the association of DEFB4_1 and DEFB4_2 with AS were 0.607 and 0.005, respectively. The results of DEFB4_2, compared with the individual having median 3 copies, those carrying ≤ 2-copies [OR = 0.68, 95%CI: (0.46, 0.99), P = 0.049; adjusted OR = 0.69, 95%CI(0.47, 1.03), P = 0.067. ]; and those carrying ≥ 4-copies [OR = 0.62, 95%CI: (0.45, 0.86), P = 0.004; adjusted OR = 0.64, 95%CI: (0.46, 0.88), P = 0.006], were significantly associated with decreasing risk of AS. Univariate analysis showed that both DEFB4_1 and DEFB4_2 were associated with Bath AS Disease Activity Index or BASDAI. After adjusted by age, sex, and disease duration, the results changed little, which demonstrated that high copies may be linked with decrease in the risk of disease severity [OR = 0.71, 95%CI: (0.56, 0.90), P = 0.005; OR = 0.75, 95%CI: (0.60, 0.94), P = 0.013, respectively]. Conclusions. The CNs of DEFB4 gene may be associated with AS and involved in disease progression.
Symbiont-Mediated Protection against Fungal Pathogens in Pea Aphids: a Role for Pathogen Specificity?

ABSTRACT Here we show that a bacterial endosymbiont, Regiella insecticola, protects pea aphids (Acyrthosiphon pisum) from the aphid-specific fungal entomopathogen Zoophthora occidentalis but not from the generalist insect fungal pathogen Beauveria bassiana. This finding highlights the complex influence of fungi on the dynamics of this economically important agricultural pest.
Regulation of Class II Expression in Monocytic Cells after HIV-1 Infection1

Human macrophage hybridoma cells were used to study HLA-DR expression after HIV-1 infection. HLA-DR surface expression was lost 2 wk after infection that was associated with decreased mRNA transcription. Transfecting HLA-DR-α and HLA-DR-β cDNA driven by a nonphysiological CMV promoter restored expression, suggesting that regulatory DNA-binding proteins may be affected by HIV-1 infection. There was no protein binding to conserved class II DNA elements (W/Z/S box, X-1 and X-2 boxes, and Y box) in a HIV-1-infected human macrophage hybridoma cell line, 43HIV, and in primary monocytes that lost HLA-DR expression after HIV-1BaL infection. PCR analysis of the HIV-1-infected cells that lost HLA-DR expression revealed mRNA for W/Z/S (RFX-5), X-1 (RFX-5), X-2 (hX-2BP), and one Y box DNA-binding protein (NF-YB), and CIITA, a non-DNA-binding protein necessary for class II transcription. There was no mRNA for the Y box-binding protein, NF-YA. However, HLA-DR expression could be restored by transfection with NF-YA driven by a CMV promoter, although HLA-DR failed to localize in either the late endosomes, lysosomes, or acidic compartments. This was associated with a loss of class II-associated invariant chain peptide and leupeptin-induced protein in the 43HIV cells. To address this further, non-HIV-1-infected 43 cells were infected with vaccinia virus containing HIV-1 gag, nef, pol, and env proteins. HLA-DR failed to localize in neither the late endosomes, lysosomes, or acidic compartments in the vaccinia-infected cells containing HIV-1 env protein. HIV-1 appears to have multiple effects on class II expression in monocytic cells that may contribute to the immune defects seen in HIV-1-infected patients.
Relationship of Antibodies to Sperm Head to Etiology of Infertility in Patients Undergoing In Vitro Fertilization/Embryo Transfer

ABSTRACT: Antibodies to sperm head (ASA‐H) are believed to impair reproduction, probably because of a reduction in fertilization of human oocytes. However, the incidence of ASA‐H in couples with different etiologies of infertility undergoing in vitro fertilization/embryo transfer (IVF/ET) is unestablished. To examine this question, the semen, serum, and follicular fluid of 11 couples with unexplained infertility and 25 couples with tubal infertility undergoing IVF/ET were tested with the immunobead binding assay to identify ASA‐H of IgA, IgG, and IgM isotypes. Comparing couples with unexplained vs. tubal infertility, 46% vs. 4% had ASA‐H of at least one isotype in female serum (P = .006), 36% vs. 4% had ASA‐H in follicular fluid (P = .023), 27% vs. 0% had ASA‐H in semen (P = .023), and 18% vs. 4% had ASA‐H in male serum (P = .022), respectively. ASA‐H were present in one or more fluids tested in 55% of patients with unexplained infertility, compared to 8% of patients with tubal infertility (P = .005). Of the six women with ASA‐H in their serum, 83% (5/6) were undergoing IVF/ET for unexplained infertility compared to 17% (1/6: P = .08) undergoing IVF/ET for tubal infertility. In summary, clinically significant ASA‐H are present in a substantial number of infertile women undergoing IVF/ET, particularly those whose infertility is unexplained. Based on these findings, we conclude that it is efficacious to screen all women with unexplained infertility undergoing IVF/ET for ASA‐H.
AMP‐ACTIVATED PROTEIN KINASE ACTIVATION AS A STRATEGY FOR PROTECTING VASCULAR ENDOTHELIAL FUNCTION

1 AMP‐activated protein kinase (AMPK) is a serine/threonine protein kinase involved in the regulation of cellular and organismal metabolism. AMPK has a heterotrimeric structure, consisting of a catalytic α‐subunit and regulatory β‐ and γ‐subunits, each of which has two or more isoforms that are differentially expressed in various tissues and that arise from distinct genes. The AMPK system acts as a sensor of cellular energy status that is conserved in all eukaryotic cells. In addition, AMPK is activated by physiological stimuli and oxidants. 2 The importance of AMPK in cardiovascular functions is best demonstrated by recent studies showing that widely used drugs, including statins, metformin and rosiglitazone, execute cardiovascular protective effects at least partly through the activation of AMPK. As a consequence, AMPK has been proposed as a candidate target for therapeutic intervention in the treatment of both Type 2 diabetes and metabolic syndrome owing to its central role in the regulation of energy balance; it may also have a role in weight control. 3 In the present brief review, we summarize the recent progress of AMPK signalling and regulation focusing on vascular endothelial cells. We further hypothesize that AMPK is a dual sensor for energy and redox status within a cell and AMPK may be a therapeutic target for protecting vascular endothelial function.
Complete cytogenetic and molecular remission in a case of lymphoid blast crisis in chronic myeloid leukemia with intensive chemotherapy and interferon alpha

To the Editor: Blast crisis (BC) of chronic myeloid leukemia (CML) is refractory to treatment and fatal in weeks to months. Only patients who have a successful bone marrow trasplantation (BMT) from a histocompatible donor can be cured. Alpha interferon (alpha-IFN) produces normalization of blood counts in 70% and cytogenetic remission in 15-20% of patients with chronic phase CML (1-2). Similar results have been recently reported in the treatment of relapse of CML in chronic phase after allogeneic bone marrow trasplantation (3). Furthermore, alpha-IFN has been reported to have produced a complete cytogenetic and molecular response in a patient relapsed with clonal evolution after bone marrow transplantation (4). We report here a patient with lymphoid BC-CML, who had a complete hematological and partial cytogenetic remission after intensive chemotherapy and, with alpha2a-IFN therapy, has obtained a complete cytogenetic and molecular remission lasting for 5 years after the BC.
Differential diagnosis of diffuse alveolar haemorrhage in immunocompromised patients

Purpose of review Diffuse alveolar haemorrhage (DAH) is a life-threatening medical emergency in immunocompromised and immunocompetent patients characterized by haemoptysis, anaemia, acute respiratory failure and diffuse pulmonary infiltrates on radiologic examination. This review describes DAH imaging features, causes and main differential diagnosis. Recent findings In immunosuppressed patients, DAH occurs most frequently in haematologic neoplasms, after haematopoietic stem cell transplantation or solid organ transplantation, secondary to drug reaction or infection, and associated with AIDS. However, differential diagnoses of all of these conditions include several conditions with similar findings. Summary Imaging patterns of DAH do not differ significantly from those of conditions included in the main differential diagnosis. The differential diagnosis depends on the patient's immunity status. In immunocompromised patients, infection and lung injury of other causes must be considered.
Factors Affecting Perceived Impact of Electronic Marketplaces

Although B2B e-commerce represents today an important business activity with stable growth, it has not grown according to initial expectations, partly due to the difficulty in measuring its performance. Recent academic literature tries to explain the motivations and behavior of companies participating in electronic markets as well as the benefits deriving from this participation. Following this stream of research, the purpose of this paper is to present the preliminary results of a field survey studing e-marketplace participation across two dimensions: The first one examines the attitude of user companies towards e-marketplace participation (motivations, goals, expectations, fears etc.). The second dimension examines the perceptions of e-marketplace participants about the impact and benefits they derive from their participation as well as the factors affecting the perceived impact. The survey was conducted using a questionnaire, among participants of five e-marketplaces (a total of 62 companies participated), allowing for comparisons both between buyers and sellers and between different types of emarketplaces. The statistical analysis of the quantitative results renders interesting findings that come to confirm or compliment existing literature and indicate concrete directions for further research. The results indicate a generic transaction-based orientation of the e-marketplace participants towards the exchange, the negative effect of external pressure on benefits perception and the importance of participating years and company size to the impact of e-marketplaces.