Miracle-dz/UniFAR-FTUs huggingface dataset:
MarR-type Transcriptional Regulator ChlR Activates Expression of Tetrapyrrole Biosynthesis Genes in Response to Low-oxygen Conditions in Cyanobacteria*

Background: Oxygen is required for three enzymatic steps in tetrapyrrole biosynthesis. Results: A transcriptional regulator gene was found by genome resequencing of a mutant of Synechocystis sp. PCC 6803. Discussion: Sll1512 (ChlR) is a MarR-type transcriptional regulator involved in induction of genes in response to low-oxygen conditions. Significance: Maintaining the chlorophyll level constant under hypoxia is important for cyanobacteria to survive. Oxygen is required for three enzyme reactions in chlorophyll and bilin biosynthesis pathways: coproporphyrinogen III oxidase (HemF), heme oxygenase (HO1), and Mg-protoporphyrin IX monomethylester cyclase (ChlAI). The cyanobacterium Synechocystis sp. PCC 6803 has alternative enzymes, HemN, HO2, and ChlAII, to supply chlorophyll/bilins even under low-oxygen environments. The three genes form an operon, chlAII-ho2-hemN, that is induced in response to low-oxygen conditions to bypass the oxygen-dependent reactions. Here we identified a transcriptional regulator for the induction of the operon in response to low-oxygen conditions. A pseudorevertant, Δho1R, was isolated from a HO1-lacking mutant Δho1 that is lethal under aerobic conditions. Δho1R grew well even under aerobic conditions. In Δho1R, HO2 that is induced only under low-oxygen conditions was anomalously expressed under aerobic conditions to complement the loss of HO1. A G-to-C transversion in sll1512 causing the amino acid change from aspartate 35 to histidine was identified as the relevant mutation by resequencing of the Δho1R genome. Sll1512 is a MarR-type transcriptional regulator. An sll1512-lacking mutant grew poorly under low-oxygen conditions with a remarked decrease in Chl content that would be caused by the suppressed induction of the chlAII and hemN genes in Chl biosynthesis under low-oxygen conditions. These results demonstrated that Sll1512 is an activator in response to low-oxygen environments and that the D35H variant becomes a constitutive activator. This hypothesis was supported by a gel shift assay showing that the Sll1512-D35H variant binds to the DNA fragment upstream of the operon. We propose to name sll1512 chlR.
Comparison of the Q-fever complement fixation test and two commercial enzyme-linked immunosorbent assays for the detection of serum antibodies against Coxiella burnetii (Q-fever) in ruminants: Recommendations for use of serological tests on imported animals in New Zealand

Abstract AIM: To make valid recommendations on the use of serological test methods for the detection of serum antibodies in ruminants against Coxiella burnetii (Q-fever), by comparing the performance of the complement fixation test (CFT) and two ELISA, and by identifying reasons for discrepancies between the test methods. METHODS: A total of 73 serum samples from infected cattle, 69 from infected goats, and 100 samples from non-infected cattle and 57 samples from non-infected sheep, as well as 95 samples from infected cattle herds (mix of seropositive and seronegative samples), were tested using the CFT, the IDEXX ELISA (I-ELISA) and the Pourquier ELISA (P-ELISA). A mixed panel of 12 serum samples from sheep from inter-laboratory proficiency testing (proficiency panel) was also tested using the CFT and both ELISA, and further investigated using IgG- and IgM-specific ELISA. RESULTS: Generally, the two commercial ELISA were more sensitive than the CFT for the detection of infected ruminants. Good agreement between ELISA for positive and negative results was found for samples from the infected herd, while results for the positive panels varied between the two ELISA. For the total of the positive serum panels, the I-ELISA detected 95% of samples as positive or suspicious, while the P-ELISA detected only 81%. In the P-ELISA, more samples were considered suspicious (18%) than in the I-ELISA (14%). All sera from noninfected sheep and cattle tested negative in the serological test methods employed, except for one positive sample from a sheep in the P-ELISA. Further investigation revealed that a CFT-positive but ELISA-negative result was due to high IgM and low IgG reactivity. CONCLUSIONS: The two commercial ELISA were more sensitive than the CFT in all panels from infected ruminants. However, they could only detect IgG. The I-ELISA should be the serological test method of choice for cattle, sheep and goats for import testing of animals into New Zealand because it was more sensitive than the P-ELISA and was equally specific to the PELISA and the CFT. For other animal species, such as deer and camelids, the CFT should still be used since none of the ELISA has been evaluated for these species. This study has shown that the two commercial ELISA will detect the majority of infected ruminants but may miss animals that have not developed an IgG response.
Limits to optical chemical sensing fluctuations versus ultimate performance

The role of chemical sensors in modern process industry cannot be overestimated, since they are encountered at different stages of process control, helping maintain product quality and at the same time allowing to keep an eye on environmental issues and pollution problems. Numerous device families are currently in use, where optical chemical sensors are probably the fastest, the simplest and the most sensitive. Affinity sensors represent a class of these devices based on adsorption of chemical analytes. The prime example are plasmonic sensors, which are label-free, ultra sensitive and ultra fast. Literature usually defines only the ideal sensitivity of such devices and their performance is taken as granted. In reality there are many parasitic processes that decrease their performance and introduce significant measurement uncertainties. Noise and fluctuations in such sensors can be generated by both extrinsic or intrinsic sources and a significant part of them is a consequence of fundamental processes that at the same time ensure the very function of the devices. The main intrinsic mechanisms include adsorption-desorption, optical flicker and thermal noise, while the level of the extrinsic noise is related with the quality of the interrogating beam source and the photo detector. In this contribution we offer a possible systematization of different sources of noise in refractometric chemical sensors and analyze the influence of such fluctuations to the ultimate device performance.
Atrial ﬁbrillation: the role of common and rare genetic variants

Atrial ﬁbrillation (AF) is the most common cardiac arrhythmia affecting 1–2% of the general population. A number of studies have demonstrated that AF, and in particular lone AF, has a substantial genetic component. Monogenic mutations in lone and familial AF, although rare, have been recognized for many years. Presently, mutations in 25 genes have been associated with AF. However, the complexity of monogenic AF is illustrated by the recent ﬁnding that both gain- and loss-of-function mutations in the same gene can cause AF. Genome-wide association studies (GWAS) have indicated that common single-nucleotide polymorphisms (SNPs) have a role in the development of AF. Following the ﬁrst GWAS discovering the association between PITX2 and AF, several new GWAS reports have identiﬁed SNPs associated with susceptibility of AF. To date, nine SNPs have been associated with AF. The exact biological pathways involving these SNPs and the development of AF are now starting to be elucidated. Since the ﬁrst GWAS, the number of papers concerning the genetic basis of AF has increased drastically and the majority of these papers are for the ﬁrst time included in a review. In this review, we discuss the genetic basis of AF and the role of both common and rare genetic variants in the susceptibility of developing AF. Furthermore, all rare variants reported to be associated with AF were systematically searched for in the Exome Sequencing Project Exome Variant Server.
Pathophysiology of chronic left ventricular dysfunction. New insights from the measurement of absolute myocardial blood flow and glucose utilization.

BACKGROUND Chronically dysfunctional myocardium may improve after coronary revascularization. This condition was thought to be due to a chronically reduced myocardial blood flow (MBF). Recently, however, it has been shown that in patients without previous infarction but with chronic left ventricular dysfunction, baseline MBF was normal. METHODS AND RESULTS To study the pathophysiology of chronic left ventricular dysfunction in patients with previous infarction, regional MBF (milliliter per minute per gram of water-perfusable tissue) and glucose utilization (MRG; micromoles per minute per gram) during hyperinsulinemic euglycemic clamp were measured with positron emission tomography in 30 patients before bypass. At baseline, 133 myocardial segments were normal, and 107 were dysfunctional. After revascularization, 59 of 107 segments improved, while 48 of 107 were unchanged. MBF was 0.92 +/- 0.25 mL.min-1.g-1 in normal segments, 0.87 +/- 0.31 mL.min-1.g-1 in improved segments (P = NS versus normal), and 0.82 +/- 0.40 mL.min-1.g-1 in unchanged segments (P < .05 versus normal). In 90% of the dysfunctional segments, MBF was > 0.42 mL.min-1.g-1, a cutoff value corresponding to the mean MBF minus 2 SD in normal segments. The MRG was 0.71 +/- 0.14 mumol.min-1.g-1 in 9 age-matched normal subjects, 0.45 +/- 0.19 mumol.min-1.g-1 (P < .01) in normal segments, 0.44 +/- 0.14 mumol.min-1.g-1 in improved segments (P = NS versus normal), and 0.34 +/- 0.17 mumol.min-1.g-1 in unchanged segments (P < .01 versus normal and improved). CONCLUSIONS The results suggest that resting MBF measured with 15O-labeled water in chronically dysfunctional segments is not reduced and that the myocardium of these patients is less sensitive to insulin than that of normal subjects.
Pioglitazone Increases Insulin Sensitivity, Reduces Blood Glucose, Insulin, and Lipid Levels, and Lowers Blood Pressure, in Obese, Insulin-Resistant Rhesus Monkeys

The antidiabetic effects of pioglitazone hydrochloride were evaluated in 6 spontaneously obese, insulin-resistant rhesus monkeys. The animals were studied during six successive 2-wk treatment phases separated by 2-wk rest periods: two placebo phases; 0.3, 1.0, and 3.0 mg · kg−1 · day−1 pioglitazone hydrochloride phases; and a final placebo phase. During the second week of each treatment phase, serum insulin (immunoreactive insulin [IRI]), plasma glucose, and serum triglyceride (TG) levels were measured after an overnight fast and after a standardized meal. Blood pressure was measured and glucose tolerance tests (modified minimal model protocol) were performed a few days after the meal tests. Pioglitazone hydrochloride significantly improved fasting and postprandial levels of IRI, plasma glucose, and TG in a dose-related manner (P < 0.05). Fasting values during treatment with 3.0 mg · kg−1 · day−1 were reduced by 64% for IRI, 19% for plasma glucose, and 44% for TG compared with the placebo phase before treatment. Efficacy of pioglitazone hydrochloride was more marked for those animals with fasting hyperglycemia. Insulin sensitivity was increased by pioglitazone hydrochloride (P = 0.05), whereas glucose effectiveness and glucose disappearance rate were not detectably affected. Systolic and mean arterial blood pressures were significantly decreased by pioglitazone hydrochloride (P < 0.05). No toxic side effects of pioglitazone hydrochloride treatment were noted.
Social Capital and Women’s Labor Force Participation in Chile

ABSTRACT Using data from Chile, this study analyzes the relationship between different forms of social capital and women’s labor force participation, accounting for both endogeneity problems and differences among women of different economic strata. First, the results suggest that only some types of social capital are relevant for labor force participation: namely, networks with weaker yet far-reaching connections, including higher-status individuals. There are neither empirical nor theoretical reasons to believe that women have better access to such networks than men. Second, this type of social capital is only relevant for the economic integration of the richest women, failing to increase labor force participation among women of the other 80 percent of households. Thus, this study concludes that policies targeted at women’s economic integration based on the presumption that women have more social capital than men are deeply flawed.
Use of mathematical model to predict hemodynamics in cavopulmonary anastomosis with persistent forward flow.

BACKGROUND The bidirectional cavopulmonary anastomosis with additional pulmonary blood flow is used as a staged procedure or a definitive palliation of univentricular hearts. In this paper the flow competition occurring between the caval and the pulmonary flows is investigated. The hemodynamics in the superior vena cava and the blood flow distribution into the lungs, as well as the systemic arterial oxygen availability, are correlated with the severity of the right ventricle outflow tract obstruction and the pulmonary arteriolar resistance. MATERIALS AND METHODS Computer models of the pre- and postoperative hemodynamics of univentricular hearts were developed. The effects of increasing severity of the right ventricle outflow tract obstruction, with a pulmonary arteriolar resistance ranging from 0.8 to 7.9 nonindexed Woods units, were simulated. RESULTS The study indicates that the presence of an additional pulmonary blood flow from the native pulmonary artery may be beneficial. Since an excessive additional blood flow may cause central venous hypertension, its optimal value should be chosen according to the value of pulmonary arteriolar resistance. The model was utilized to simulate four clinical cases. CONCLUSIONS The simulations show that the model can predict the postoperative hemodynamics and could therefore be usefully applied to predict quantitatively the effect of the native pulmonary blood flow following bidirectional cavopulmonary anastomosis.
Getting weights to behave themselves: achieving stability and performance in neural-adaptive control when inputs oscillate

Local basis functions offer computational efficiency when used in nonlinear adaptive control schemes. However, commonly used robust weight (parameter) update methods do not result in acceptable performance when applied to underdamped systems. This is because persistent oscillation in the inputs encourages severe weight drift, in turn requiring large robust terms that significantly limit the performance. In particular, the methods of leakage, c-modification, dead/one, and weight projection sacrifice performance to halt this weight drift. In contrast, it is observed (in simulations) that application of the proposed method halts the weight drift without sacrificing the performance.
Alterations in calcium signaling and a decrease in Bcl‐2 expression: Possible correlation with apoptosis in aged striatum

Aging is a multifaceted process associated with various functional and structural deficits that might be evolved in degenerative diseases. It has been shown that neurodegenerative disorders are associated with alterations in Ca2+ homeostasis. Thus, in the present work, we have investigated Ca2+ signaling and apoptosis in aged striatum. Our results show that glutamate and NMDA evoke a greater Ca2+ rise in striatum slices from aged animals. However, this difference is not present when glutamate is tested in the absence of external Ca2+. Immunostaining of glutamate receptors shows that only NMDA receptors (NR1) are increased in the striatum of aged rats. Increases in mitochondrial Ca2+ content and in the reactive oxygen species levels were also observed in aged animals, which could be associated with tissue vulnerability. In addition, a decrease in the Bcl‐2 protein expression and an enhancement in apoptosis were also present in aged striatum. Together the results indicate that, in aged animals, alterations in Ca2+ handling coupled to an increase in ROS accumulation and a decrease in the prosurvival protein Bcl‐2 may contribute to apoptosis induction and cell death in rat striatum. © 2009 Wiley‐Liss, Inc.
IS186 Insertion at a Hot Spot in thelon Promoter as a Basis for Lon Protease Deficiency ofEscherichia coli B: Identification of a Consensus Target Sequence for IS186 Transposition

ABSTRACT The radiation sensitivity of Escherichia coli B was first described more than 50 years ago, and the genetic locus responsible for the trait was subsequently identified aslon (encoding Lon protease). We now show that bothE. coli B and the first reported E. coliK-12 lon mutant, AB1899, carry IS186insertions in opposite orientations at a single site in thelon promoter region and that this site represents a natural hot spot for transposition of the insertion sequence (IS) element. Our analysis of deposited sequence data for a number of other IS186 insertion sites permitted the deductions that (i) the consensus target site sequence for IS186transposition is 5′-(G)≥4(N)3–6(C)≥4-3′, (ii) the associated host sequence duplication varies within the range of 6 to 12 bp and encompasses the N(3–6) sequence, and (iii) in a majority of instances, at least one end of the duplication is at the G-N (or N-C) junction. IS186-related sequences were absent in closely related bacterium Salmonella entericaserovar Typhimurium, indicating that this IS element is a recent acquisition in the evolutionary history of E. coli.
Incidence and perceptions of “qualified” accounts filed by small charities

ABSTRACT Charities filing accounts with the Charity Commission for England and Wales have been asked since 2014 whether their accounts are qualified. It was found that 96% of charities (£100k–250k income) stating that their accounts were qualified had mis-answered the question. This was explored further with charity personnel and funders supporting small charities: the notion of qualified accounts was found to be misunderstood both by operational charities and by their funders. This raises issues regarding use of data on the Charity Commission’s Register and for charity regulation, as the Commission indicates that qualified reports are a trigger for possible regulatory investigation. HIGHLIGHTS 96% of charities, stating to the regulator they have qualified accounts, do not Term “qualified accounts” misunderstood by small charities and funders Funders seek charity accounting compliance information from regulator Regulator’s website displays inaccurate information on charities’ qualified accounts Funders unlikely to dismiss a small charity solely on basis of qualified accounts
The Deep Roots of Protectionism in the Southern Cone: Constituent Interests and Mercosur’s Common External Tariff

Abstract This article examines the influence of subnational economic interests on the formation of supranational trade policy in the Southern Common Market (Mercosur). Accounting for differences in the relative importance of member countries, the article argues that subnational economic interests influenced the structure of Mercosur’s common external tariff (CET). Although the CET was negotiated without direct input from voters or legislators, its structure reflects the interests of geographically specific economic interests in the member countries. The results of a regression analysis of tariffs toward nonmembers indicate that the economic composition of subnational political jurisdictions shaped the structure of the CET. These findings suggest that by overlooking subnational economic interests, much of the current literature on the evolution of Mercosur misses a critical aspect of the policymaking process.
Modification of post-myocardial infarction granulocyte-colony stimulating factor therapy with myelo-suppressives.

BACKGROUND The purpose of the present study was to investigate the effect of granulocyte colony-stimulating factor (G-CSF) in combination with myelo-suppressives on post-myocardial infarction (MI) myocardial repair. METHODS AND RESULTS Twenty-four hours after 30-min ischemia and reperfusion (day 0), rabbits were assigned to 4 treatment groups: myelo-suppressives (M group), G-CSF (G group), the 2 in combination (MG group) or saline (S group). Significantly greater numbers of circulating stem cells were seen in the MG group than in the G group, with attenuated leukocytosis. In addition, MG caused the greatest upregulation of stromal cell-derived factor (SDF)-1 within the infarcted myocardium and thus recruitment of stem cells from the circulation into the infarcted tissue. This led to enhanced myocardial repair, as indicated by the numbers of bone marrow cell-derived cardiomyocytes and endothelial cells, reduction in scar tissue, improvement in cardiac function and reduction in left ventricular remodeling during the chronic phase of MI. These beneficial effects were entirely abolished by the administration of a CXCR4 antagonist AMD3100, which indicates the importance of CXCR4/SDF-1-axis as a mechanism underlying myocardial repair. CONCLUSION The combination of G-CSF and myelo-suppressives may be a useful new therapy that overcomes the insufficiency seen with G-CSF alone.
A population-based study of depressive symptoms in multiple sclerosis in Stockholm county: association with functioning and sense of coherence

Objectives: To explore and analyse the prevalence of depressive symptoms in people with multiple sclerosis (PwMS), taking into account disease-related and sociodemographic factors, and also to analyse the association between depressive symptoms and functioning (tested and self-reported) and sense of coherence (SOC), respectively. Methods: Home visits were made to a population-based sample of 166 PwMS. Data were obtained from structured, face-to-face interviews using the Beck Depression Inventory (BDI), the Sickness Impact Profile (SIP) and the SOC scale. A range of tests were also carried out for analyses of different aspects of functioning such as cognitive function, walking capacity and manual dexterity, and structured interviews examined activities of daily living and frequency of social/lifestyle activities. Results: 19% (28/149) of the people were depressed (BDI ⩾13). Depressive symptoms were associated with worse self-reported functioning on the SIP and with poor memory function, but not with any of the other tests of functioning. Depressive symptoms were associated with weak SOC, but not with any of the disease-related or sociodemographic factors studied. Conclusion: The prevalence of depressive symptoms in a population-based sample of PwMS is high. Given the serious nature of depression and its association with worse self-reported functioning and weak SOC, attention to, and treatment of, mental-health problems and depression are strongly indicated in the clinical management of multiple sclerosis.
In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs

The effect of a tea fortified with five herbs selected from Indian traditional medicine (Ayurveda) for their putative immunoenhancing effect (Withania somnifera, Glycyrrhzia glabra, Zingiber officinale, Ocimum sanctum and Elettaria cardamomum) on innate immunity was investigated. Ex vivo natural killer (NK) cell activity was assessed after consumption of fortified tea compared with regular tea in two independent double‐blind intervention studies. Both studies were conducted in India with healthy volunteers (age ≥ 55 years) selected for a relatively low baseline NK cell activity and a history of recurrent coughs and colds. In a pilot study conducted with 32 volunteers, the consumption of Natural Care tea significantly improved the NK cell activity of the volunteers in comparison with a population consuming regular tea. These results were validated in an independent crossover study with 110 volunteers. Data from these two studies indicate that regular consumption of the tea fortified with Ayurvedic herbs enhanced NK cell activity, which is an important aspect of the (early) innate immune response to infections. Copyright © 2009 John Wiley & Sons, Ltd.