Miracle-dz/UniFAR-FTUs huggingface dataset:
Gibberella xylarioides Sensu Lato from Coffea canephora: a New Mating Population in the Gibberella fujikuroi Species Complex

ABSTRACT Gibberella xylarioides Heim & Saccas (presumed anamorph, Fusarium xylarioides Steyaert) is the causal agent of coffee wilt disease, an economically important tracheomycosis in Africa. In vitro crosses carried out with Congolese, Ugandan, and Tanzanian single-ascospore/conidial isolates originating from diseased Coffea canephora/excelsa demonstrated a heterothallic mating system, controlled by a single locus with two alleles, MAT-1 and MAT-2. Compatible isolates produced fertile perithecia within 2 to 8 weeks after mating. Mating type (MAT) was characterized by PCR with primer pairs previously developed for the Gibberella fujikuroi species complex (GFC) and for Fusarium oxysporum. All strains analyzed were morphologically identical and corresponded to Booth's description of the “female” F. xylarioides strain. Based on crossing results and MAT-2/translation elongation 1-α (tef) sequence data, G. xylarioides, as currently understood, is demonstrated to encompass at least three “groups”: G. xylarioides sensu strictu Ia, defined hitherto by two “historical” West African strains originating from the severe 1930s to 1950s epidemic (CBS 25852 and CBS 74979); G. xylarioides sensu strictu Ib, defined by two “historical” Central African lowland strains (DSMZ 62457 and ATCC 15664); and G. xylarioides sensu lato II, containing Congolese, Ugandan, and Tanzanian C. canephora/excelsa isolates. Infertility of crosses between the coffee wilt pathogen and known GFC mating populations demonstrates that G. xylarioides sensu lato constitutes a new biological species within the G. fujikuroi complex. MUCL 44532/MUCL 43887 and MUCL 35223/MUCL 44549 are proposed as G. xylarioides sensu lato II MAT-1/MAT-2 reference mating type tester strains.
Molecular characterisation of enteroinvasive Escherichia coli O136:K78 isolates from patients of a diarrhoea outbreak in China

Purpose: A diarrhoea outbreak occurred in a kindergarten, which caused 21 relevant infected cases. Our object was to confirm the pathogens and their molecular characterisation. Materials and Methods: Faecal samples from 21 patients were collected on the 3rd day after their symptom onset, and a regular epidemiological investigation was conducted. Bacterial isolation was performed in accordance with standard laboratory protocol, serological and molecular characterisations were determined by serum agglutination test and real-time polymerase chain reaction (PCR) method, respectively. The pulsed field gel electrophoresis (PFGE) and 16S rRNAs were conducted to determine the homology. Results: Eleven enteroinvasive Escherichia coli (EIEC) O136:K78 strains were isolated. The serum agglutination test showed that all strains' serotypes were E. coli (EIEC) O136:K78. Real-time PCR showed that 10 (91%) strains carried the invasion plasmid antigen H gene (ipaH), carried by all four Shigella species and EIEC. The strain that didn't carry the ipaH gene had different biochemical reactions of L-lizyna and L-rhamnose with the other strains. The complete 16S rRNA sequences showed 98.4% identity between ipaH-negative isolate and the others, and the PFGE indicated that the ipaH-negative isolate was not homological with other isolates in this diarrhoea outbreak. Conclusions: The diarrhoea outbreak was caused by E. coli (EIEC) O136:K78.
Detection of unrecognized low‐level mtDNA heteroplasmy may explain the variable phenotypic expressivity of apparently homoplasmic mtDNA mutations

Mitochondrial DNA (mtDNA) mutations are an important cause of human disease. Most mtDNA mutations are found in heteroplasmy, in which the proportion of mutant vs. wild‐type species is believed to explain some of the observed high phenotypic heterogeneity. However, homoplasmic mutations also observe phenotypic heterogeneity, which may be in part due to undetected low levels of heteroplasmy. In the present report, we have developed two assays, using DHPLC and Pyrosequencing (Biotage AB, Uppsala, Sweden), for reliably and accurately detecting low‐level mtDNA heteroplasmy. Using these assays we have identified a three‐generation family segregating two mtDNA mutations in heteroplasmy: the deafness‐related m.1555A>G mutation in the 12S rRNA gene (MTRNR1) and a new variant (m.15287T>C) in the cytochrome b gene (MTCYB). Both heteroplasmic mtDNA mutations are transmitted through generations in a random manner, thus showing differences in mutation load between siblings within the family. In addition, the developed assays were also used to screen a group of deaf subjects of unknown etiology for the presence of heteroplasmy for both mtDNA variants. Two additional heteroplasmic m.1555A>G samples, previously considered as homoplasmic, and two deaf subjects carrying m.15287T>C variant were identified, thus confirming the high specificity and reliability of the approach. The development of assays for reliably detecting low‐level heteroplasmy, together with the study of heteroplasmic mtDNA transmission, are essential steps for a better knowledge and clinical management of mtDNA diseases. Hum Mutat 29(2), 248–257, 2008. © 2007 Wiley‐Liss, Inc.
Protocol-Based Resuscitation Bundle to Improve Outcomes in Septic Shock Patients: Evaluation of the Michigan Health and Hospital Association Keystone Sepsis Collaborative*

Objectives:To evaluate the impact of a multi-ICU quality improvement collaborative implementing a protocol-based resuscitation bundle to treat septic shock patients. Design:A difference-in-differences analysis compared patient outcomes in hospitals participating in the Michigan Health & Hospital Association Keystone Sepsis collaborative (n = 37) with noncollaborative hospitals (n = 50) pre- (2010–2011) and postimplementation (2012–2013). Collaborative hospitals were also stratified as high (n = 19) and low (n = 18) adherence based on their overall bundle adherence. Setting:Eighty-seven Michigan hospitals with ICUs. Patients:We compared 22,319 septic shock patients in collaborative hospitals compared to 26,055 patients in noncollaborative hospitals using the Michigan Inpatient Database. Interventions:Multidisciplinary ICU teams received informational toolkits, standardized screening tools, and continuous quality improvement, aided by cultural improvement. Measurements and Main Results:In-hospital mortality and hospital length of stay significantly improved between pre- and postimplementation periods for both collaborative and noncollaborative hospitals. Comparing collaborative and noncollaborative hospitals, we found no additional reductions in mortality (odds ratio, 0.94; 95% CI, 0.87–1.01; p = 0.106) or length of stay (–0.3 d; 95% CI, –0.7 to 0.1 d; p = 0.174). Compared to noncollaborative hospitals, high adherence hospitals had significant reductions in mortality (odds ratio, 0.84; 95% CI, 0.79–0.93; p < 0.001) and length of stay (–0.7 d; 95% CI, –1.1 to –0.2; p < 0.001), whereas low adherence hospitals did not (odds ratio, 1.07; 95% CI, 0.97–1.19; p = 0.197; 0.2 d; 95% CI, –0.3 to 0.8; p = 0.367). Conclusions:Participation in the Keystone Sepsis collaborative was unable to improve patient outcomes beyond concurrent trends. High bundle adherence hospitals had significantly greater improvements in outcomes, but further work is needed to understand these findings.
Electrical stimulation of the auditory nerve: direct current measurement in vivo

Neural prostheses use charge recovery mechanisms to ensure the electrical stimulus is charge balanced. Nucleus cochlear implants short all stimulating electrodes between pulses in order to achieve charge balance, resulting in a small residual direct current (DC). In the present study the authors sought to characterize the variation of this residual DC with different charge recovery mechanisms, stimulation modes, and stimulation parameters, and by modeling, to gain insight into the underlying mechanisms. In an acute study with anaesthetised guinea pigs, DC was measured in four platinum intracochlear electrodes stimulated using a Nucleus(R) CI24M cochlear implant at moderate to high pulse rates (1200-14 500 pulses/s) and stimulus intensities (0.2-1.75 mA at 26-200 /spl mu/s/phase). Both monopolar and bipolar stimulation modes were used, and the effects of shorting or combining a capacitor with shorting for charge recovery were investigated. Residual DC increased as a function of stimulus rate, stimulus intensity, and pulse width. DC was lower for monopolar than bipolar stimulation, and lower still with capacitively coupled monopolar stimulation. The authors' model suggests that residual DC is a consequence of Faradaic reactions which allow charge to leak through the electrode tissue interface. Such reactions and charge leakage are still present when capacitors are used to achieve charge recovery, but anodic and cathodic reactions are balanced in such a way that the net charge leakage is zero.
Sevoflurane speeds recovery of baroreflex control of heart rate after minor surgical procedures compared with isoflurane.

UNLABELLED Volatile anesthetics attenuate arterial baroreflex functions, whereas noxious stimuli may modify baroreflex-induced circulatory responses during anesthesia. We designed the present study to compare baroreflex control of heart rate during sevoflurane and isoflurane anesthesia in young healthy surgical patients. Baroreflex sensitivity was assessed in 24 patients randomized to receive either sevoflurane (n = 12) or isoflurane (n = 12) for general anesthesia. After an 8- to 10-h fast and no premedication, measurements of RR intervals obtained from electrocardiography and systolic blood pressure (SBP) measured through a radial artery catheter were made at conscious baseline (Awake), during end-tidal sevoflurane 2% or isoflurane 1.2% plus 67% nitrous oxide before incision (Anesth), during surgery at end-tidal sevoflurane 2% or isoflurane 1.2% plus 67% nitrous oxide (Surg), and 20 min after tracheal extubation (Recov). Baroreflex responses were triggered by bolus i.v. injections of phenylephrine (100-150 micrograms) and nitroprusside (100-150 micrograms) to increase and decrease SBP by 15-30 mm Hg, respectively. The linear portions of the baroreflex curves relating RR intervals and SBP were determined to obtain baroreflex sensitivities. Baroreflex sensitivities to both pressor and depressor tests were significantly depressed during Anesth and Surg periods compared with Awake values in both anesthetic techniques. The pressor test sensitivity during the Recov period returned to the Awake value after sevoflurane (12.9 +/- 3.7 vs 11.0 +/- 8.7 ms/mm Hg [mean +/- SD]) but was still depressed after isoflurane anesthesia (13.9 +/- 8.0 vs 4.8 +/- 3.2 ms/mm Hg; P < 0.05). The depressor test sensitivities during the Recov period remained depressed after both anesthetic techniques. We conclude that both sevoflurane and isoflurane depress arterial baroreflex function during anesthesia and surgery, but the pressor test sensitivity was restored more quickly after sevoflurane than after isoflurane anesthesia. IMPLICATIONS Arterial baroreflex function is an important neural control system for maintaining cardiovascular stability. We found that baroreflex control of heart rate due to hypertensive perturbation returned to the preanesthetic level more quickly after sevoflurane than after isoflurane anesthesia.
Comparative Analysis of Functional Assays for Characterization of Agonist Ligands at G Protein-Coupled Receptors

A variety of functional assays are available for agonist or antagonist screening of G protein-coupled receptors (GPCRs), but it is a priori not predictable which assay is the most suitable to identify agonists or antagonists of GPCRs with therapeutic value in humans. More specifically, it is not known how a given set of GPCR agonists compares in different functional assays with respect to potency and efficacy and whether the level of the signaling cascade that is analyzed has any impact on the detection of agonistic responses. To address this question, the authors used the recently cloned human S1P5 receptor as a model and compared a set of 3 lipid ligands (sphingosine 1-phosphate [S1P], dihydro sphingosine 1-phosphate [dhS1P], and sphingosine) in 5 different functional assays: GTPγS binding, inhibition of adenylyl cyclase activity, mobilization of intracellular Ca2+ via the FLIPR and aequorin technology, and MAP kinase (ERK1/2) activation. S1P induced agonistic responses in all except the ERK1/2 assays with EC50 values varying by a factor of 10. Whereas dhS1P was identified as a partial agonist in the GTPγS assay, it behaved as a full agonist in all other settings. Sphingosine displayed partial agonistic activity exclusively in GTPγS binding assays. The findings suggest that assays in a given cellular background may vary significantly with respect to suitability for agonist finding and that ligands producing a response may not readily be detectable in all agonist assays. (Journal of Biomolecular Screening 2003:500-510)
Cardiac function in Wilms' tumor survivors.

PURPOSE To study late cardiac function in a single diagnostic group (children with Wilms' tumor) with good long-term survival; to compare patients treated with anthracyclines (doxorubicin) with patients treated without anthracyclines and with a normal child/adolescent group; and to examine the risk factors involved in late cardiac dysfunction. PATIENTS AND METHODS Echocardiographic studies were performed on 97 Wilms' tumor patients treated with anthracyclines (mean cumulative dose, 303 mg/m2) with a mean follow-up time of 7.1 years, on 39 Wilms' tumor patients treated without anthracyclines with a mean follow-up time of 8.9 years, and on 50 normal subjects. Left ventricular (LV) dimensions, end systolic wall stress (a measure of afterload), and load-dependent and -independent measures of contractility were compared between groups. Potential risk factors, including age at diagnosis, follow-up duration, sex, pubertal status, cardiac irradiation, dose-intensity, and cumulative dose of anthracyclines, were studied by multivariate analysis. RESULTS Twenty-five percent of the anthracycline-treated group showed cardiac abnormalities. All but one of these patients had increased LV afterload. Risk factors for increased afterload were anthracycline cumulative dose (P < .05) and anthracycline dose-intensity (P < .02). Wilms' tumor patients treated without anthracyclines had thickened LV walls compared with normal subjects (P < .05). CONCLUSION Total dose and dose-intensity of anthracycline were risk factors for increased LV afterload in long-term Wilms' tumor survivors treated on standard protocols. The increase in afterload accounted for reduced LV shortening, whereas contractility was rarely abnormal. The new finding that Wilms' tumor survivors who do not receive anthracyclines have mild LV hypertrophy may provide some protection against anthracycline-induced cardiotoxic effects.
Efficacy of metformin for prevention of weight gain in psychiatric populations: a review

There is uncertainty with regard to the appropriate use of metformin for the prevention and management of second-generation antipsychotic-induced weight gain and metabolic abnormalities. We aim to systematically review the primary literature and to provide recommendations with regard to the use of metformin in psychiatric populations prescribed second-generation antipsychotics. The authors undertook a literature search of Medline, EMBASE, and PsycINFO using the search terms; antipsychotic OR atypical antipsychotic AND weight AND metformin. Narrative review was undertaken without additional statistical analysis. The search provided 198 results from which 10 original research papers were identified: six randomized controlled trials and one open-label study for adults and two randomized controlled trials and one open-label study for children and adolescents. Four meta-analyses were also identified. We concluded that if weight gain occurs after second-generation antipsychotic initiation, despite lifestyle intervention, metformin should be considered. Further studies with adequate statistical power are required to determine the efficacy of metformin in those with chronic psychotic illness.
Mutational Analysis of the Saccharomyces cerevisiae Cytochrome c Oxidase Assembly Protein Cox11p

ABSTRACT Cox11p is an integral protein of the inner mitochondrial membrane that is essential for cytochrome c oxidase assembly. The bulk of the protein is located in the intermembrane space and displays high levels of evolutionary conservation. We have analyzed a collection of site-directed and random cox11 mutants in an effort to further define essential portions of the molecule. Of the alleles studied, more than half had no apparent effect on Cox11p function. Among the respiration deficiency-encoding alleles, we identified three distinct phenotypes, which included a set of mutants with a misassembled or partially assembled cytochrome oxidase, as indicated by a blue-shifted cytochrome aa3 peak. In addition to the shifted spectral signal, these mutants also display a specific reduction in the levels of subunit 1 (Cox1p). Two of these mutations are likely to occlude a surface pocket behind the copper-binding domain in Cox11p, based on analogy with the Sinorhizobium meliloti Cox11 solution structure, thereby suggesting that this pocket is crucial for Cox11p function. Sequential deletions of the matrix portion of Cox11p suggest that this domain is not functional beyond the residues involved in mitochondrial targeting and membrane insertion. In addition, our studies indicate that Δcox11, like Δsco1, displays a specific hypersensitivity to hydrogen peroxide. Our studies provide the first evidence at the level of the cytochrome oxidase holoenzyme that Cox1p is the in vivo target for Cox11p and suggest that Cox11p may also have a role in the response to hydrogen peroxide exposure.
The Loss of γH2AX Signal is a Marker of DNA Double Strand Breaks Repair Only at Low Levels of DNA Damage

The induction of DNA double-strand breaks (DSBs) by genotoxic treatment leads to hightoxicity and genetic instability. Various approaches have been undertaken to quantify thenumber of breaks and to follow the kinetic of DSB repair. Recently, the phosphorylation ofthe variant histone H2AX (named γH2AX), quantified by specific immunodetectionapproaches, has provided a valuable and highly sensitive method to monitor DSBs formation.Although it is admitted that the number of γH2AX foci reflected that of DSBs, contradictoryreports leave open the question of a link between the disappearance of γH2AX signal andDSBs repair. We determined γH2AX expression (i) in cells either proficient or not in DSBsrepair capacity, (ii) after exposure to ionizing radiation (IR) or calicheamicin γ1, aradiomimetic compound, (iii) and by three different immunodetection methods, focinumbering, flow cytometry or Western blotting. We showed here that γH2AX loss correlateswith DSB repair activity only at low cytotoxic doses, when less than 100-150 DSBs breaksper genome are produced, independently of the method used. In addition, in DNA repairproficient cells, the early decrease in the number and intensity of γH2AX foci observed after a2 Gy exposure was not associated with a significant change in the global γH2AX level asdetermined by Western blotting or flow cytometry. These results suggest that thedephosphorylation step of γH2AX may be limiting and that the loss of foci is mediated notonly by γH2AX dephosphorylation but also through its redistribution towards the chromatin.
Normative sleep data, cognitive function and daily living activities in older adults in the community.

STUDY OBJECTIVES To present normative data of sleep-wake characteristics and to examine risk factors associated with extreme values (i.e., in the 5 lower and upper percentiles of the distribution) in older adults. DESIGN Cross-sectional telephone survey SETTING The metropolitan area of Paris, France. PARTICIPANTS A total of 7010 randomly selected households were contacted. Among them, 1264 households included at least 1 resident 60 years of age or older; 1026 subjects agreed to participate (participation rate: 80.9%). INTERVENTIONS None. MEASUREMENTS AND RESULTS Subjects were interviewed with the Sleep-EVAL System about their sleeping habits and sleep and psychiatric disorders. In addition, the system administered to all the participants the Psychological General Well-Being Schedule, the Cognitive Difficulties Scale (Mac Nair-R), and an independent living scale. The median nighttime sleep duration was 7 hours without significant difference between the age groups. Factors positively associated with the 5 percentile (4 hours 30 minutes or less) of nighttime sleep duration were obesity, poor health, insomnia, and insomnia accompanied by daytime sleepiness and cognitive impairment. At the other extremity (95th percentile), long sleep (9 hours 30 minutes or more) was associated with organic disease, lack of physical exercise, and lower education. A daytime sleep duration of 1 hour or more (95th percentile) was associated with being a man, cognitive impairment, high blood pressure, obesity, and insomnia. Long sleep latency (95th percentile at 80 minutes) was associated with anxiety, lower education, poor health, insomnia without excessive daytime sleepiness, and obstructive sleep apnea syndrome. Obesity and loss of autonomy in activities of daily living was associated with both early (9 PM or earlier) and late bedtime (1 AM or later) and early (< or = 5 AM) and late (> or = 9 AM) wake-up time. CONCLUSIONS This study illustrates the usefulness of normal distributions of sleep parameters in the general population to calculate different risk factors associated with extreme values of the normal distribution.
Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen

The aim of the present work was to investigate the synergistic effect between toll-like receptor (TLR) 3 ligand polyinosinic:polycytidylic acid (pI:C) and TLR5 ligand flagellin (FLN) on immune responses induced by nasally delivered hepatitis B virus surface antigen (HBsAg). Mannan and chitosan oligosaccharide-modified, pH-responsive poly(lactic-co-glycolic acid) (MC-PLGA) microparticles (MPs) containing HBsAg, FLN, pI:C or both ligands were prepared with a double-emulsion method. In vitro uptake experiments show that cellular uptake of MC-PLGA MPs by macrophages was through energy-dependent, receptor-mediated endocytosis mechanism. After uptake of MPs by macrophages, MC-PLGA MPs existed both in the endo-some and in the cytoplasm. FLN and pI:C in solution or MP formulation could synergize to activate macrophages and induce higher pro-inflammatory cytokines interleukin (IL)-6, IL-12, interferon-γ and anti-inflammatory cytokines IL-10 compared to single TLR ligand (P<0.05). In vivo immunogenicity studies indicated that co-delivery of FLN and pI:C within MC-PLGA MPs synergistically induced higher serum anti-HBsAg IgG levels and Th1 cytokine levels compared with MC-PLGA MPs encapsulated single TLR ligand plus MPs encapsulated HBsAg (P<0.05). These results suggest that synergic TLR3 and TLR5 stimulation might be a promising novel tool for nasally delivered HBsAg.