Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Tumor Necrosis Factor Alpha Expression and Release from Peritoneal Mouse Macrophages In Vitro in Response to Proliferating Gram-Positive versus Gram-Negative Bacteria

ABSTRACT Viable Escherichia coli and Staphylococcus aureus bacteria elicited markedly different in vitro tumor necrosis factor alpha (TNF-α) responses when placed in coculture with peritoneal murine macrophages. These include quantitative differences in TNF-α mRNA expression and corresponding protein product secretion as well as kinetic differences in the profiles of the TNF-α responses. Further, lipopolysaccharide (from E. coli) is a major contributing factor to these differences, as revealed by comparative experiments with endotoxin-responsive (C3Heb/FeJ) and endotoxin-hyporesponsive (C3H/HeJ) macrophages. Nevertheless, the eventual overall magnitude of the TNF-α secretion of macrophages in response to S. aureus was at least equivalent to that observed with E. coli, while appearing at time periods hours later than the E. coli-elicited TNF-α response. Both the magnitude and kinetic profile of the TNF-α responses were found to be relatively independent of the rate of bacterial proliferation, at least to the extent that similar results were observed with both viable and paraformaldehyde-killed microbes. Nevertheless, S. aureus treated in culture with the carbapenem antibiotic imipenem manifests markedly altered profiles of TNF-α response, with the appearance of an early TNF-α peak not seen with viable organisms, a finding strikingly similar to that recently reported by our laboratory from in vivo studies (R. Silverstein, J. G. Wood, Q. Xue, M. Norimatsu, D. L. Horn, and D. C. Morrison, Infect. Immun. 68:2301–2308, 2000). In contrast, imipenem treatment of E. coli-cocultured macrophages does not significantly alter the observed TNF-α response either in vitro or in vivo. In conclusion, our data support the concept that the host inflammatory response of cultured mouse macrophages in response to viable gram-positive versus gram-negative microbes exhibits distinctive characteristics and that these distinctions are, under some conditions, altered on subsequent bacterial killing, depending on the mode of killing. Of potential importance, these distinctive in vitro TNF-α profiles faithfully reflect circulating levels of TNF-α in infected mice. These results suggest that coculture of peritoneal macrophages with viable versus antibiotic-killed bacteria and subsequent assessment of cytokine response (TNF-α) may be of value in clarifying, and ultimately controlling, related host inflammatory responses in septic patients.
Control of Phenotypic Plasticity Via Regulatory Genes

What is the form of genetic ontrol of phenotypic plasticity? Are there specific loci determining plastic responses (Bradshaw 1965; Schlichting 1986; Scheiner and Lyman 1989, 1991), or is plasticity simply an epiphenomenon of selection for different trait means in different environments (Via and Lande 1985; Via 19.87)? This central issue in a long-standing dispute is of fundamental importance because the mechanism of genetic control of plasticity will determine the long-term dynamics, rates, and constraints on the evolution of reaction norms. Via (1993) reiterates her view that there is no need to invoke separate loci controlling the shape of reaction norms: phenotypic plasticity is not a trait itself but merely a by-product of evolution at numerous loci to produce appropriate trait means in different environments. Without presenting new empirical evidence, she observes that "current models illustrate how phenotypic plasticity can evolve . without requiring the existence of separate 'genes for plasticity' " (pp. 352-353). To avoid semantic wrangling, we define plasticity genes as regulatory loci that exert environmentally dependent control over structural gene expression and thus produce a plastic response. Such loci represent a genetic mechanism for plastic response that is distinct from that assumed in quantitative genetic models of reaction norm evolution. We have the following disagreements with Via's (1993) viewpoint. (1) There is a wealth of evidence for the existence of plasticity genes as defined above. (2) The evolution of adaptive plasticity involves two processes: (i) adjustment of the available quantitative genetic variation to approach the phenotypic optimum and (ii) development of new genetic machinery for controlling response to the environment. (3) The argument that current statistical models can explain the evolution of plasticity avoids the issue that similar statistical results may be produced by means of very different genetic mechanisms. 1. The existence of plasticity genes. -Two types of genetic control of phenotypic plasticity have been proposed (Schmalhausen 1949; Smith-Gill 1983; Dragavtsev and Aver'yanova 1984). (i) Allelic sensitivity is the case in which in different environments all loci are expressed, but individual alleles vary in their sensitivity, that is, there are direct effects of the environment on structural gene expression. With allelic sensitivity we expect gradual changes in phenotype, proportional to the environmental gradient. (ii) Regulatory control is the scenario in which not all gene loci are expressed in each environment, that is, gene expression is mediated through the action of regulatory loci that can control the expression of multiple structural genes. For the simplest case of regulatory control, distinct phenotypes will be produced on each side of an environmental hreshold.
Archelosaurian Color Vision, Parietal Eye Loss, and the Crocodylian Nocturnal Bottleneck

Vertebrate color vision has evolved partly through the modification of five ancestral visual opsin proteins via gene duplication, loss, and shifts in spectral sensitivity. While many vertebrates, particularly mammals, birds, and fishes, have had their visual opsin repertoires studied in great detail, testudines (turtles) and crocodylians have largely been neglected. Here I examine the genomic basis for color vision in four species of turtles and four species of crocodylians, and demonstrate that while turtles appear to vary in their number of visual opsins, crocodylians experienced a reduction in their color discrimination capacity after their divergence from Aves. Based on the opsin sequences present in their genomes and previous measurements of crocodylian cones, I provide evidence that crocodylians have co-opted the rod opsin (RH1) for cone function. This suggests that some crocodylians might have reinvented trichromatic color vision in a novel way, analogous to several primate lineages. The loss of visual opsins in crocodylians paralleled the loss of various anatomical features associated with photoreception, attributed to a “nocturnal bottleneck” similar to that hypothesized for Mesozoic mammals. I further queried crocodylian genomes for nonvisual opsins and genes associated with protection from ultraviolet light, and found evidence for gene inactivation or loss for several of these genes. Two genes, encoding parietopsin and parapinopsin, were additionally inactivated in birds and turtles, likely co-occurring with the loss of the parietal eye in these lineages.
Polyethylene Wear After Total Hip Arthroplasty: The Effect of a Modular Femoral Head with an Extended Flange-Reinforced Neck*

The use of modular components in total hip arthroplasty has been thought to contribute to accelerated polyethylene wear. Specifically, a modular femoral head with a flange extension and a longer neck may cause increased wear. The purpose of the current study was to evaluate the effect of a flange extension on polyethylene wear. Ninety-one patients who had had a total of 100 primary total hip arthroplasties were evaluated after an intermediate duration of follow-up. All of the acetabular components consisted of a hemispherical titanium-alloy fiber-mesh porous-coated shell with a nonelevated modular polyethylene liner; they were inserted without cement and with use of supplemental screws through the dome after so-called line-to-line reaming. All of the femoral components consisted of a modular head with a diameter of twenty-eight millimeters and either a long neck (with a flange extension) or a short or medium neck (without a flange extension). The study group comprised sixty-two patients (sixty-six hips) who had had radiographic evaluation that was adequate to allow the valid measurement of polyethylene wear. Thirty-two hips were in men, and thirty-four were in women. The mean age of the patients was fifty-six years, the mean weight was seventy-three kilograms, and the mean duration of follow-up was 6.1 years (range, four to eight years). The rate of polyethylene wear in the eleven hips in which the femoral component had a flange extension was significantly greater than that in the fifty-five in which the femoral component did not have a flange extension (mean, 0.17 compared with 0.11 millimeter per year; p = 0.009). Multivariate analysis showed that the presence of a flange extension was associated with increased polyethylene wear to a greater degree (F = 2.86) than were all other variables that were measured, including a younger age (F = 1.72), a more vertical angle of the acetabular component (F = 0.49), a heavier weight (F = 0.14), male gender (F = 0.11), and a smaller initial thickness of the polyethylene (F = 0.02). These data support an association between the presence of a modular femoral head with a flange extension and an accelerated rate of polyethylene wear. The presumed mechanism is an increase in peripheral, or so-called rim, impingement of the flange-reinforced neck on the acetabulum due to a decrease in the ratio between the diameters of the femoral head and neck.
Auditory intensity discrimination in the parakeet (Melopsittacus undulatus).

Three parakeets were trained by a method of avoidance conditioning to respond to intensity differences in successsively occurring tone bursts. Intensity difference limens were obtained at six sensation levels of a 2.86 kHz tone. The relative intensity difference limens (ΔI) for the parakeet were larger than similarly reported measures for man and other mammals at all sensation levels tested. Calculations of the Weber fractions at each sensation level tested showed that Weber’s law holds for the parakeet at sensation levels above 50 dB.Subject Classification: 80.50; 65.75, 65.50.
Rotating stall control via bifurcation stabilization

Rotating stall is a fundamental aerodynamic instability in axial flow compressors, induced by nonlinear bifurcation. It significantly reduces the performance of aeroengines. In this paper classical bifurcation theory is used to derive output feedback control laws in which throttle position is employed as actuator and pressure rise as output measurement. The challenge to the proposed control system is that the critical mode of the linearized system corresponding to rotating stall is neither controllable nor observable. Using the projection method, it is shown that the proposed control system is effective for elimination of rotating stall for the third-order Moore-Greitzer model.
Order Reduction using Modified Pole Clustering and Pade Approximations

The authors present a mixed method for reducing the order of the large-scale dynamic systems. In this method, the denominator polynomial of the reduced order model is obtained by using the modified pole clustering technique while the coefficients of the numerator are obtained by Pade approximations. This method is conceptually simple and always generates stable reduced models if the original high-order system is stable. The proposed method is illustrated with the help of the numerical examples taken from the literature. Keywords—Modified pole clustering, Order reduction, Pade approximation, Stability, Transfer function
Cardiolipin synthase expression is essential for growth at elevated temperature and is regulated by factors affecting mitochondrial development

Cardiolipin (CL) is a unique dimeric phospholipid localized primarily in the mitochondrial membrane. In eukaryotes, the enzyme CL synthase catalyses the synthesis of CL from two lipid substrates, CDP‐diacylglycerol and phosphatidylglycerol. In earlier studies, we reported the purification of CL synthase from Saccharomyces cerevisiae and the cloning of the gene CRD1 (previously called CLS1) that encodes the enzyme. Because CL is an important component of the mitochondrial membrane, knowledge of its regulation will provide insight into the biogenesis of this organelle. To understand how CL synthesis is regulated, we analysed CRD1 expression by Northern blot analysis of RNA extracted from cells under a variety of growth conditions. CRD1 expression is regulated by mitochondrial development factors. CRD1 levels were 7‐ to 10‐fold greater in stationary than in logarithmic growth phase, and threefold greater in wild‐type than in ρ0 mutants. Expression was somewhat elevated during growth in glycerol/ethanol versus glucose media. In contrast, CRD1 expression was not regulated by the phospholipid precursors inositol and choline, and was not altered in the regulatory mutants ino2, ino4 and opi1. Mutations in cytochrome oxidase assembly, which led to reduced Crd1p enzyme activity, did not affect CRD1 expression. The crd1 null mutant makes a truncated CRD1 message. Although the null mutant can grow on both fermentable and non‐fermentable carbon sources at lower temperatures, it cannot form colonies at 37°C. In conclusion, CRD1 expression is controlled by factors affecting mitochondrial development, but not by the phospholipid precursors inositol and choline. Expression of CRD1 is essential for growth at elevated temperatures, suggesting that either CL or Crd1p is required for an essential cellular function.
Young Investigator Award

Synaptic dysfunction leads to neurodegeneration observed in agerelated disorders such as Alzheimer’s disease (AD). The disease presents itself with two distinguishing features in terms of its pathogenesis, the neurofibrillary tangles and the amyloid plaques. These plaques contain the b-amyloid peptide (Ab), which either in the plaque-associated form or in its soluble oligomeric form is thought to set in a cascade of events that eventually leads to neurodegeneration. The reduction of amyloid, even in small measures, has been shown to alleviate the disease, and is the basis for much of the research. The neurotoxic Ab peptide is derived from a large type I transmembrane protein, the amyloid precursor protein (APP). APP is cleaved sequentially by band c-secretases leading to the formation of the Ab peptide. The key players in the processing of APP, i.e., band c-secretase and APP itself, are all membrane associated and hence are subjected to regulation by the lipid environment and membrane trafficking. Our work showed that these amyloidogenic cleavages occur in early endosomes followed by the routing of the cleaved products to multivesicular endosomes. Subsequently, Ab peptides can be released from the cells via the novel exosomal pathway. Exosomal proteins were found to accumulate in the plaques of AD patient brains suggesting a role in the pathogenesis of AD. Moreover, targeting a transient-state analog, b-secretase inhibitor to endosomes inhibited the secretase more efficiently than its soluble counterpart suggesting a novel therapeutic strategy. Extending the use of membrane-anchored inhibitors, we have now identified new structural features in the bsecretase. In addition, employing functional genomics combined with network analysis, we have uncovered several novel genes involved in the metabolism of APP. Such integrated systems biology approaches, we believe, would further our understanding of Alzheimer’s disease in terms of etiology, diagnosis and intervention. 170
Breakthrough Technologies A Virus-Induced Assay for Functional Dissection and Analysis of Monocot and Dicot Flowering Time Genes 1

Research Centre for Plant RNA Signaling, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036, China (C.Q., W.C., J.S., L.C., K.Z., C.Y., P.Z., N.S., Y.H.); Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China (Q.C.); Centre for Plant Biology and MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China (Y.L.); and Warwick-Hangzhou RNA Signaling Joint Laboratory, School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK (F.A, C.L., S.J., Y.H.)
Sepsis syndrome in Croatian intensive care units: piloting a national comparative clinical database.

AIM To assess the incidence of sepsis in selected intensive care units (ICUs) in Croatia, isolates from blood cultures, and sepsis outcomes, and to compare the results with those from other European countries. METHODS In the pilot phase of the national comparative clinical database project, we included 24 ICUs--general, specialized, neonatal, pediatric, and adult--18 from university hospitals, 3 from county hospitals, and 4 from city hospitals. By retrospective chart review, trained data collectors abstracted the data on the case mix, management strategies, and outcomes in patients consecutively admitted to ICUs. Central validation for incomplete, illogical, or inconsistent values is regularly performed to improve accurateness. RESULTS Of 5293 patients treated in 24 ICUs from November 1, 2004, to October 31, 2005, 456 (8.6%) were treated for sepsis syndrome or severe sepsis. The most common isolates from positive blood cultures were Esherichia coli (11.6%), Pseudomonas species (9.9%), and methicillin-resistant Staphylococcus aureus (9.3%). With the mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 10.0 and Sequential Organ Failure Assessment (SOFA) score of 2.4, the overall mortality for sepsis syndrome, severe sepsis, and septic shock was 29%, 35%, and 34%, respectively. When compared to university hospitals and county hospitals, city hospitals with the smallest gravitating population had significantly lower APACHE II and SOFA scores, but significantly higher mortality. CONCLUSIONS Overall mortality of patients with sepsis syndrome in Croatian ICUs was high, but outcomes of their treatment were comparable with those in other European countries. Better education in triage and treatment strategies is needed, including better implementation of Surviving Sepsis Campaign guidelines.
A gas chromatograph for quantification of peroxycarboxylic nitric anhydrides calibrated by thermal dissociation cavity ring-down spectroscopy

Abstract. The peroxycarboxylic nitric anhydrides (PANs, molecular formula: RC(O)O2NO2) can readily be observed by gas chromatography (PAN-GC) coupled to electron capture detection. Calibration of a PAN-GC remains a challenge, because the response factors differ for each of the PANs, and because their synthesis in sufficiently high purity is non-trivial, in particular for PANs containing unsaturated side chains. In this manuscript, a PAN-GC and its calibration using diffusion standards, whose output was quantified by blue diode laser thermal dissociation cavity ring-down spectroscopy (TD-CRDS), are described. The PAN-GC peak areas correlated linearly with total peroxy nitrate (ΣPN) mixing ratios measured by TD-CRDS (r > 0.96). Accurate determination of response factors required the concentrations of PAN impurities in the synthetic standards to be subtracted from ΣPN. The PAN-GC and its TD-CRDS calibration method were deployed during ambient air measurement campaigns in Abbotsford, BC, from 20 July to 5 August 2012, and during the Fort McMurray Oil Sands Strategic Investigation of Local Sources (FOSSILS) campaign at the AMS13 ground site in Fort McKay, AB, from 10 August to 5 September 2013. The PAN-GC limits of detection for PAN, PPN, and MPAN during FOSSILS were 1, 2, and 3 pptv, respectively. For the Abbotsford data set, the PAN-GC mixing ratios were compared, and agreed with those determined in parallel by thermal dissociation chemical ionization mass spectrometry (TD-CIMS). Advantages and disadvantages of the PAN measurement techniques used in this work and the utility of TD-CRDS as a PAN-GC calibration method are discussed.
Surgery for clival lesions: open resection versus the expanded endoscopic endonasal approach.

OBJECT Clival lesions pose significant challenges with regard to their surgical management. The expanded endoscopic endonasal (EEE) approach is a promising minimally invasive technique for lesions of the central skull base. The authors' aim in the current paper was to discuss the surgical treatment of clival lesions and to present the technical details, indications, and limitations of the EEE approach. Data from a recent endoscopically treated group will be compared with findings in a previous cohort of patients treated via classic open anterior and lateral approaches. METHODS Since June 2005, 17 patients with clival lesions underwent surgery via the EEE approach. Suitable candidates were chosen according to lesion characteristics, clinical parameters, and surgical goals. Neurological outcomes, Karnofsky Performance Scale scores, the extent of lesion resection, and complications were evaluated among these patients. Eighteen percent of the patients in the endoscopic group presented with recurrent disease. Another series of 43 patients, who had undergone resection of clival lesions via an anterior (rhinotomy, maxillectomy, microscopic transsphenoidal surgery, or transoral surgery) or lateral (pterional, frontoorbitozygomatic, or combined suprainfratentorial retrosigmoid) approach, was similarly reviewed. Twenty-three of these patients (53%) presented with recurrent disease and thus had undergone prior surgery. RESULTS Following the EEE approach, 11 (79%) of 14 patients who had presented with neurological symptoms experienced improvement, and gross-total resection was achieved in 59% of the patients and subtotal removal in 41%. Complications included CSF leakage (24%), tension pneumocephalus (6%), and intracranial hematoma (6%). The patient with the latter complication was the only one who experienced permanent neurological worsening. In the open resection group, neurological worsening occurred in 33% of the patients (14 of 43). Total and grosstotal removals were achieved in 84% of patients and subtotal removal in 14%. CONCLUSIONS The EEE approach has been shown to be a safe and effective technique for the resection of clival lesions with limited lateral extension. The choice of surgical approach must be tailored according to both patient and tumor characteristics. Although the 2 patient series featured in this paper are not comparable-because of a selection bias-higher rates of neurological morbidity and total and gross-total resections were observed in the open resection group. Given the long survival of some patients, the EEE approach should be favored whenever reasonable.