Miracle-dz/UniFAR-FTUs huggingface dataset:
Long‐term effects of the antibacterial agent triclosan on marine periphyton communities

Triclosan is a widely used antibacterial agent that has become a ubiquitous contaminant in freshwater, estuary, and marine environments. Concerns about potential adverse effects of triclosan have been described in several recent risk assessments. Its effects on freshwater microbial communities have been well studied, but studies addressing effects on marine microbial communities are scarce. In the present study, the authors describe short‐ and long‐term effects of triclosan on marine periphyton (microbial biofilm) communities. Short‐term effects on photosynthesis were estimated after 60 min to 210 min of exposure. Long‐term effects on photosynthesis, chlorophyll a fluorescence, pigment content, community tolerance, and bacterial carbon utilization were studied after exposing periphyton for 17 d in flow‐through microcosms to 0.316 nM to 10 000 nM triclosan. Results from the short‐term studies show that triclosan is toxic to periphyton photosynthesis. Half maximal effective concentration (EC50) values of 1080 nM and 3000 nM were estimated using 14CO2‐incorporation and pulse amplitude modulation (PAM) fluorescence measurements, respectively. After long‐term triclosan exposure in flow‐through microcosms, photosynthesis estimated using PAM fluorometry was not inhibited by triclosan concentrations up to 1000 nM but instead increased with increasing triclosan concentration. Similarly, at exposure concentrations of 31.6 nM and higher, triclosan caused an increase in photosynthetic pigments. At 316 nM triclosan, the pigment amounts were increased by a factor of 1.4 to 1.9 compared with the control level. Pollution‐induced community tolerance was observed for algae and cyanobacteria at 100 nM triclosan and higher. Despite the widespread use of triclosan as an antibacterial agent, the compound did not have any effects on bacterial carbon utilization after long‐term exposure. Environ Toxicol Chem 2015;34:2067–2077. © 2015 SETAC
Global analysis of protein aggregation in yeast during physiological conditions and arsenite stress

ABSTRACT Protein aggregation is a widespread phenomenon in cells and associated with pathological conditions. Yet, little is known about the rules that govern protein aggregation in living cells. In this study, we biochemically isolated aggregation-prone proteins and used computational analyses to identify characteristics that are linked to physiological and arsenite-induced aggregation in living yeast cells. High protein abundance, extensive physical interactions, and certain structural properties are positively correlated with an increased aggregation propensity. The aggregated proteins have high translation rates and are substrates of ribosome-associated Hsp70 chaperones, indicating that they are susceptible for aggregation primarily during translation/folding. The aggregation-prone proteins are enriched for multiple chaperone interactions, thus high protein abundance is probably counterbalanced by molecular chaperones to allow soluble expression in vivo. Our data support the notion that arsenite interferes with chaperone activity and indicate that arsenite-aggregated proteins might engage in extensive aberrant protein–protein interactions. Expression of aggregation-prone proteins is down-regulated during arsenite stress, possibly to prevent their toxic accumulation. Several aggregation-prone yeast proteins have human homologues that are implicated in misfolding diseases, suggesting that similar mechanisms may apply in disease- and non-disease settings.
Preclinical studies of chemotherapy and radiation therapy for pancreatic carcinoma

The use of radiation therapy combined with 5‐fluorouracil (5‐FU) in the treatment of pancreatic cancer has been well established. It has been hypothesized that any benefit from combined 5‐FU and radiation has been due to radiosensitization. Improved therapy could result from a better understanding of the mechanism of radiosensitization and the development of compounds capable of providing better radiosensitization. This article reviews preclinical findings on the mechanism of cytotoxicity and radiosensitization for 5‐FU, fluorodeoxyuridine, thymidine analogs, and gemcitabine (2′,2′‐difluorodeoxycytidine) and discusses the clinical implications of these findings. Cancer 1996;78:674‐9.
Photosynthetic Bradyrhizobia Are Natural Endophytes of the African Wild Rice Oryza breviligulata

ABSTRACT We investigated the presence of endophytic rhizobia within the roots of the wetland wild rice Oryza breviligulata, which is the ancestor of the African cultivated rice Oryza glaberrima. This primitive rice species grows in the same wetland sites as Aeschynomene sensitiva, an aquatic stem-nodulated legume associated with photosynthetic strains ofBradyrhizobium. Twenty endophytic and aquatic isolates were obtained at three different sites in West Africa (Senegal and Guinea) from nodal roots of O. breviligulata and surrounding water by using A. sensitiva as a trap legume. Most endophytic and aquatic isolates were photosynthetic and belonged to the same phylogenetic Bradyrhizobium/Blastobacter subgroup as the typical photosynthetic Bradyrhizobium strains previously isolated from Aeschynomene stem nodules. Nitrogen-fixing activity, measured by acetylene reduction, was detected in rice plants inoculated with endophytic isolates. A 20% increase in the shoot growth and grain yield of O. breviligulata grown in a greenhouse was also observed upon inoculation with one endophytic strain and one Aeschynomene photosynthetic strain. The photosynthetic Bradyrhizobium sp. strain ORS278 extensively colonized the root surface, followed by intercellular, and rarely intracellular, bacterial invasion of the rice roots, which was determined with a lacZ-tagged mutant of ORS278. The discovery that photosynthetic Bradyrhizobium strains, which are usually known to induce nitrogen-fixing nodules on stems of the legume Aeschynomene, are also natural true endophytes of the primitive rice O. breviligulatacould significantly enhance cultivated rice production.
The late gestation fetal cardiovascular response to hypoglycaemia is modified by prior peri‐implantation undernutrition in sheep

Undernourished late gestation fetuses display asymmetric growth restriction, suggestive of a redistribution of nutritional resources. The modification of fetal organ blood supply in response to acute hypoxia is well characterized, but it is not known whether similar responses occur in response to acute reductions in nutrition, or if such late gestation responses can be influenced by early gestation nutrition. In pregnant sheep, total nutrient requirements were restricted during the peri‐implantation period (PI40, 40%; PI50, 50% of total, days 1–31) or in late gestation (L, 50% total, days 104–postmortem). Control animals were fed 100% nutrient requirements. Fetal organ blood flows were measured at baseline, and during acute fetal hypoglycaemia induced by maternal insulin infusion at 125 dGA. Baseline heart rate was increased in PI40 fetuses. During hypoglycaemia, an initial rise in fetal heart rate was followed by a slower fall. Fetal femoral artery blood flow decreased, and adrenal blood flow and femoral vascular resistance increased in all fetuses during hypoglycaemia. These changes were accompanied by increased fetal plasma adrenaline and cortisol, and reduced plasma insulin levels. The maximum femoral artery blood flow response to hypoglycaemia occurred earlier in PI50 and PI40 compared with control fetuses. The late gestation fetal cardiovascular response to acute hypoglycaemia was consistent with a redistribution of combined ventricular output away from the periphery and towards central organs. One element of the peripheral vascular response was modified by peri‐implantation nutrient restriction, indicating that nutritional challenges early in gestation can have an enduring impact on cardiovascular control.
Cardiac ryanodine receptors control heart rate and rhythmicity in adult mice.

AIMS The molecular mechanisms controlling heart function and rhythmicity are incompletely understood. While it is widely accepted that the type 2 ryanodine receptor (Ryr2) is the major Ca(2+) release channel in excitation-contraction coupling, the role of these channels in setting a consistent beating rate remains controversial. Gain-of-function RYR2 mutations in humans and genetically engineered mouse models are known to cause Ca(2+) leak, arrhythmias, and sudden cardiac death. Embryonic stem-cell derived cardiomyocytes lacking Ryr2 display slower beating rates, but no supporting in vivo evidence has been presented. The aim of the present study was to test the hypothesis that RYR2 loss-of-function would reduce heart rate and rhythmicity in vivo. METHODS AND RESULTS We generated inducible, tissue-specific Ryr2 knockout mice with acute ∼50% loss of RYR2 protein in the heart but not in other tissues. Echocardiography, working heart perfusion, and in vivo ECG telemetry demonstrated that deletion of Ryr2 was sufficient to cause bradycardia and arrhythmia. Our results also show that cardiac Ryr2 knockout mice exhibit functional and structural hallmarks of heart failure, including sudden cardiac death. CONCLUSION These results illustrate that the RYR2 channel plays an essential role in pacing heart rate. Moreover, we find that RYR2 loss-of-function can lead to fatal arrhythmias typically associated with gain-of-function mutations. Given that RYR2 levels can be reduced in pathological conditions, including heart failure and diabetic cardiomyopathy, we predict that RYR2 loss contributes to disease-associated bradycardia, arrhythmia, and sudden death.
Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. The molecular mechanisms involved in the progression of IPF are not fully understood; however, the platelet-derived growth factor (PDGF)/PDGF receptor pathway is thought to play a critical role in fibrogenesis of the lungs. Other growth factors, including fibroblast growth factor and vascular endothelial growth factor, are also thought to contribute to the pathogenesis of pulmonary fibrosis. Nintedanib is an inhibitor of multiple tyrosine kinases, including receptors for PDGF, fibroblast growth factor, and vascular endothelial growth factor. In the Phase II TOMORROW trial, treatment with 150 mg of nintedanib twice daily showed a trend to slow the decline in lung function and significantly decrease acute exacerbations in patients with IPF, while showing an acceptable safety profile. The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 trial, the time to the first acute exacerbation significantly increased in IPF patients who were treated with 150 mg of nintedanib twice daily. Pirfenidone, another antifibrotic drug, was shown to limit the decline in pulmonary function in patients with IPF in the ASCEND trial. Combination therapy with nintedanib and pirfenidone is anticipated, although further evaluation of its long-term safety is needed. There is limited evidence for the safety of the combination therapy although a Phase II trial conducted in Japan demonstrated that combination therapy with nintedanib and pirfenidone was tolerable for 1 month. Available antifibrotic agents (ie, pirfenidone and N-acetylcysteine) have limited efficacy as single therapies for IPF; therefore, further study of combination therapy with antifibrotic agents is needed.
SNC-Meister: Admitting More Tenants with Tail Latency SLOs

Meeting tail latency Service Level Objectives (SLOs) in shared cloud networks is both important and challenging. One primary challenge is determining limits on the multi-tenancy such that SLOs are met. Doing so involves estimating latency, which is difficult, especially when tenants exhibit bursty behavior as is common in production environments. Nevertheless, recent papers in the past two years (Silo, QJump, and PriorityMeister) show techniques for calculating latency based on a branch of mathematical modeling called Deterministic Network Calculus (DNC). The DNC theory is designed for adversarial worst-case conditions, which is sometimes necessary, but is often overly conservative. Typical tenants do not require strict worst-case guarantees, but are only looking for SLOs at lower percentiles (e.g., 99th, 99.9th). This paper describes SNC-Meister, a new admission control system for tail latency SLOs. SNC-Meister improves upon the state-of-the-art DNC-based systems by using a new theory, Stochastic Network Calculus (SNC), which is designed for tail latency percentiles. Focusing on tail latency percentiles, rather than the adversarial worst-case DNC latency, allows SNC-Meister to pack together many more tenants: in experiments with production traces, SNC-Meister supports 75% more tenants than the state-of-the-art.
Large deletions of the KCNV2 gene are common in patients with cone dystrophy with supernormal rod response

Cone dystrophy with supernormal rod response (CDSRR) is considered to be a very rare autosomal recessive retinal disorder. CDSRR is associated with mutations in KCNV2, a gene that encodes a modulatory subunit (Kv8.2) of a voltage‐gated potassium channel. In this study, we found that KCNV2 mutations are present in a substantial fraction (2.2–4.3%) of a sample of 367 independent patients with a variety of initial clinical diagnoses of cone malfunction, indicating that CDSRR is underdiagnosed and more common than previously thought. In total, we identified 20 different KCNV2 mutations; 15 of them are novel. A new finding of this study is the substantial proportion of large deletions at the KCNV2 locus that accounts for 15.5% of the mutant alleles in our sample. We determined the breakpoints and size of all five different deletions, which ranged between 10.9 and 236.8 kb. Two deletions encompass the entire KCNV2 gene and one also includes the adjacent VLDLR gene. Furthermore, we investigated N‐terminal amino acid substitution mutations for its effect on interaction with Kv2.1 using yeast two‐hybrid technology. We found that these mutations dramatically reduce or abolish this interaction suggesting a lack of assembly of heteromeric Kv channels as one underlying pathomechanism of CDSRR. 32:1398–1406, 2011. ©2011 Wiley Periodicals, Inc.
Effect of rotation on the stability of side-heated buoyant convection between infinite horizontal walls

This paper deals with buoyant convection generated by a horizontal gradient of temperature in an inﬁnite ﬂuid layer, which is known as Hadley circulation, and studies the effects induced by applying a rotation around the vertical axis. First, the basic ﬂow proﬁle withrotationisderivedandtheinﬂuenceoftherotationisdepicted:Theoriginallongitudinal velocity proﬁle is decreased in intensity when rotation is applied and its structure is progressively changed, whereas a transverse velocity component is created, which increases with the rotation intensity, overcomes the longitudinal velocity, and eventually decreases. Different asymptotic behaviors for these proﬁles have also been highlighted. The stability of these ﬂows is then studied. The effects of the Prandtl number, the Taylor number, and the thermal boundary conditions are highlighted for the three types of instability occurring in such a situation (shear, oscillatory, and Rayleigh instabilities). It is observed that they are all stabilized by the rotation and that the increase of the critical thresholds is accompanied by a spinning of the wave vector corresponding to a progressive change of the orientation of the marginal perturbation rolls. Energy budgets are ﬁnally used to analyze the instability mechanisms.
Effectiveness of Corporate Intranet in Selected Malaysian Companies

This study was undertaken with the purpose of measuring intranet effectiveness in selected Malaysian companies. Defining effectiveness as composite constructs of intranet characteristics, intranet usage and individual performance, the study employed a cross-sectional survey method. A total of 359 users participated in the study. The intranet characteristics namely, task fit, information quality and systems quality are found to be significantly related to intranet usage. Likewise the three intranet variables, namely, usage mode, usage for decision support and usage for knowledge sharing are also found to be significantly related to individual performance measured in terms of task innovation, task productivity and personal sense of accomplishment. Hence, the study had indeed confirmed that intranets users in Malaysian companies have perceived their intranet to be effective.
Positional editing of transmembrane domains during ion channel assembly

Summary The integration of transmembrane (TM)-spanning regions of many channels and ion transporters is potentially compromised by the presence of polar and charged residues required for biological function. Although the two TMs of the ATP-gated ion channel subunit P2X2 each contain charged/polar amino acids, we found that each TM is efficiently membrane inserted when it is analysed in isolation, and uncovered no evidence for cooperativity between these two TMs during P2X2 integration. However, using minimal N-glycosylation distance mapping, we find that the positioning of TM2 in newly synthesized P2X2 monomers is distinct from that seen in subunits of the high-resolution structures of assembled homologous trimers. We conclude that P2X2 monomers are initially synthesised at the endoplasmic reticulum in a distinct conformation, where the extent of the TM-spanning regions is primarily defined by the thermodynamic cost of their membrane integration at the Sec61 translocon. In this model, TM2 of P2X2 subsequently undergoes a process of positional editing within the membrane that correlates with trimerisation of the monomer, a process requiring specific polar/charged residues in both TM1 and TM2. We postulate that the assembly process offsets any energetic cost of relocating TM2, and find evidence that positional editing of TM2 in the acid-sensing ion channel (ASIC1a) is even more pronounced than that observed for P2X2. Taken together, these data further underline the potential complexities involved in accurately predicting TM domains. We propose that the orchestrated repositioning of TM segments during subunit oligomerisation plays an important role in generating the functional architecture of active ion channels, and suggest that the regulation of this underappreciated biosynthetic step may provide an elegant mechanism for maintaining ER homeostasis.
Hepatic Steatosis: Assessment with Acoustic Structure Quantification of US Imaging.

PURPOSE To investigate the diagnostic performance of acoustic structure quantification (ASQ) for the assessment of hepatic steatosis by using hydrogen 1 ((1)H) magnetic resonance (MR) spectroscopy as the reference standard and to compare ASQ with hepatorenal ratio. MATERIALS AND METHODS This prospective study was approved by an institutional review board, and informed written consent was obtained from all participants. ASQ and MR spectroscopy were performed in 89 participants (mean age, 41.48 years ± 14.16; 35 men, 54 women) without history of chronic liver disease. Obtained were focal disturbance (FD) ratio by using ASQ, hepatic fat fraction (HFF) by using MR spectroscopy, and hepatorenal ratio by using a histogram. Correlation coefficient, intraclass correlation coefficient, and receiver operating curve analyses were performed. RESULTS FD ratio measured with ASQ had a strong linear correlation with HFF measured with MR spectroscopy after logarithmic transformation of both variables (r = -0.87; P < .001). By using HFF of 5.79% as a cutoff value of 10% hepatic steatosis, 29 of 89 participants (32.6%) were categorized into the group with hepatic steatosis of 10% or greater (mean HFF, 13.18% ± 4.89). The area under curve of the FD ratio for diagnosing hepatic steatosis 10% or greater was 0.959 (95% confidence interval: 0.895, 0.990) with sensitivity of 86.2% (95% confidence interval: 68.3%, 96.0%) and specificity of 100% (95% confidence interval: 94.0%, 100.0%) by using a cutoff value of 0.1; the area under curve and specificity of the FD ratio were significantly higher than those of the hepatorenal ratio (respectively, 0.772 and 73.3%; respective P values, .001 and <.001). CONCLUSION This pilot study in a cohort of patients with hepatic steatosis without other parenchymal disease suggested ASQ may be valuable for the quantification of hepatic steatosis and detection of hepatic steatosis 10% or greater in living liver donors.
Persistence of song types in Darwin's finches, Geospiza fortis, over four decades

Learned bird songs evolve via cultural evolution, with song patterns transmitted across generations by imitative learning. In Darwin's finches of the Galápagos Islands, males learn songs from their fathers, and song types can be maintained across multiple generations. However, little is known about the time frame over which specific song types are preserved, in the face of copy errors and corresponding modifications to song structure. Here we investigate cultural evolution in songs of male Geospiza fortis, at Academy Bay, Santa Cruz Island, comparing songs recorded in 1961 by R. Bowman (20 individuals) to those recorded in 1999 by J. Podos (16 individuals). For each individual, we characterized four timing and six frequency parameters, and assessed inter-individual variation in song structure using multivariate analysis. Several 1961 song types persisted into 1999, some with remarkable fidelity. Variation among song types was extensive during both years, and we detected no changes in 10 vocal parameters across the sampling period. These results illustrate temporal continuity in a culturally acquired trait, and raise questions about mechanisms that promote stability in song structure.
Cytokine imbalance and autoantibody production in T cell receptor-alpha mutant mice with inflammatory bowel disease

Spontaneous inflammatory bowel disease (IBD) resembling human ulcerative colitis develops in mice mutant for the T cell receptor alpha gene (TCR-alpha-/-). TCR-alpha-/- mice lack TCR-alpha/beta+ cells but contain TCR-gamma/delta+ cells and a small population of a unique CD4+, TCR-alpha-/beta+(low) cells. Since all the immunoglobulin (Ig) classes are present in these mice, help to B cells must be provided by cells other than TCR-alpha/beta+ cells. In the present study, we found serum levels of IgG1 and IgG2 to be markedly increased in TCR-alpha-/- mice with IBD as compared to TCR-alpha-/- mice without IBD or TCR- alpha+/- controls. An increase in IgG1-, IgG2a- and IgA- but not IgM- secreting mesenteric lymph node (MLN) B cells was detected in TCR-alpha- /- mutant mice. There was also a marked increase in MLN B cells secreting autoantibody (IgG) to tropomyosin, a cytoskeletal protein. Examination of the hyperplastic MLN showed a marked increase in the number of B, TCR-delta+, and CD4+ TCR-alpha-/beta+ cells, similar to the cell population observed at the site of colonic inflammation. Analysis of spontaneous cytokine production by MLN cells using an enzyme-linked immunospot assay, immunohistochemistry, and reverse transcription/polymerase chain reaction showed a decrease of interleukin 2 (IL-2) but a marked increase of IL-4 and interferon gamma (IFN-gamma) production in TCR-alpha-/- mice with IBD as compared to TCR- alpha-/- mice without IBD and TCR alpha+/- control mice. Both TCR-alpha- /beta+ and TCR-delta+ cells were found to be capable of producing IL-4; IFN-gamma was produced mostly by non-T cells, many of which were shown to be CD3- NK 1.1+ cells. We propose that the cytokine imbalance present in these mice results in expansion of B cells, production and switching of autoantibodies to IgG2 subclass, and development of IBD. It is possible that the unusual CD4+ TCR-alpha-/beta+ population and expanded TCR-gamma/delta+ population present in TCR-alpha-/- mice plays a central role in this abnormal immune response.