Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced Concentrations of Soluble Adhesion Molecules after Antioxidant Supplementation in Postmenopausal Women with High Cardiovascular Risk Profiles – A Randomized Double-Blind Study

Background: One of the suggested mechanisms of increased cardiovascular risk in postmenopause is a loss of the antioxidant effects of estrogens. It has been shown that classical cardiovascular risk factors increase oxidative stress on the arterial wall, and that endothelial cells react to this insult by increased expression of cellular adhesion molecules (CAM), which in turn are markers of arterial wall inflammation. Methods: A randomized, placebo-controlled, double-blind study was performed in 60 postmenopausal women with high cardiovascular risk profiles, but free from clinical atherosclerotic disease. Patients were randomized to either antioxidant supplementation (using a combination of natural antioxidants; n = 30) or placebo (n = 30), and followed for 12 weeks. The concentrations of the adhesion molecules sVCAM-1 and sICAM-1 were measured by ELISA at baseline and at the end of the study, as well as total cholesterol, LDL, HDL, triglycerides and blood pressure. Results: 27 women in the antioxidant supplementation group and 29 on placebo completed the study. At baseline, there were no significant differences in measured parameters between the groups: sICAM-1 concentrations were 341.8 ± 116.9 vs. 349.9 ± 104.6 ng/ml (active treatment vs. placebo; p = n.s.) and sVCAM-1 concentrations were 780.5 ± 325.8 vs. 761.0 ± 333.7 ng/ml (p = n.s.). In contrast, at the end of the study, sICAM-1 concentrations were 301.6 ± 56.0 vs. 356.0 ± 134.8 ng/ml (active treatment vs. placebo; p = 0.053) and sVCAM-1 concentrations were 656.0 ± 326.5 vs. 818.5 ± 381.0 ng/ml (p = 0.04). There were no significant differences between or changes within the groups in measured cholesterol and blood pressure. Conclusion: Antioxidant supplementation reduces serum concentrations of endothelium-derived adhesion molecules sICAM-1and sVCAM-1 in postmenopausal women with high cardiovascular risk profiles.
Haptics in Music: The Effects of Vibrotactile Stimulus in Low Frequency Auditory Difference Detection Tasks

We present an experiment that investigated the effect of vibrotactile stimulation in auditory pitch discrimination tasks. Extra-auditory information was expected to have some influence upon the frequency discrimination of auditory Just Noticeable Difference (JND) detection levels at 160 Hz. To measure this, the potential to correctly identified positive and negative frequency changes for two randomly divided groups was measured and then compared. The first group was given an audio only JND test and the second group was given the same test, but with additional vibrotactile stimulus delivered via a vibrating glove device. The results of the experiment suggest that in musical interactions involving the selection of specific pitches, or the detection of pitch variation, vibrotactile feedback may have some advantageous effect upon a musician's ability to perceive changes when presented in synchrony with auditory stimulus.
The effects of external sodium substitution on cell sodium and potassium in vascular smooth muscle

1. The entry of Li into the vascular smooth muscle cells of the rat tail artery follows first‐order kinetics with a rate constant of approximately 1·3 hr−1 at 10 m M‐[Li]o. The rate constant decreases gradually to ca. 0·5 hr−1 when the [Li]o/[Na]o ratio is increased.
The Science Behind Powerful Questioning: A Systemic Questioning Framework for Coach Educators and Practitioners

At the heart of the coaching process is the core competency of questioning, often referred to as powerful questioning. Coach educators and trainers diligently teach students the importance of asking questions (versus giving advice) during coaching sessions and teach them to structure questions appropriately (such as using open versus closed-ended questions). Still, coaching students struggle with knowing what questions to ask and when during their work with clients. Although many students search for a list of so-called magic coaching questions, I contend that coaches instead need a framework of questioning to use when coaching a client. A questioning framework could help educators teach the science of questioning as a means for developing coaches’ professional judgment, thereby helping coaches make better-informed choices about what types of questions to ask clients during coaching sessions. This paper presents an evidence-based conceptual framework called the Systemic Questioning Framework. Application of the framework during a coaching conversation may increase the coach’s confidence and competence when making decisions regarding how to shape questions in the moment in response to the client, enabling better coaching outcomes.
Human androgenic steroids affect growth of dermatophytes in vitro

Summary. Hormonal effects on fungal growth are of particular interest to medical mycology. In the skin, androgenic steroids metabolized within pilosebaceous units may have direct effects on dermatophytes that invade hair follicles. In this study, 10‐1to 102mg 1‐1testosterone, 5‐α‐dihydrotestosterone, dehydroepiandrosterone, androstenedione and androstanedione were used in agar dilution assays to test their effects on thallus diameters of Trichophyton rubrum, Epidermophyton floccosum, T. tonsurans, T. mentagrophytes and Microsporum canis. All dermatophytes responded in a dose‐dependent manner with reduced diameters of thalli. Growth of T. rubrum and E. floccosum was completely or strongly suppressed by 102mg 1‐1rostenedione and androstanedione. A minor inhibition of all strains was obtained with 101to 102mg 1‐1testosterone, dehydroepiandrosterone and 5‐α‐dihydrotes‐tosterone, the last being least inhibitory for all species. Trichophyton mentagrophytes and M. canis were least responsive to most hormones. The high susceptibility of T. rubrum and E. floccosum to intrafollicular androstenedione and androstanedione could be one reason why these two species are unable to cause tinea capitis. Receptor‐mediated effects and an unspecific interference with fungal sterol metabolism are discussed as mechanisms of fungal inhibition by steroidal hormones.
Description of Laccomimus gen. n. and eleven new species from the Neotropical region (Coleoptera, Dytiscidae, Laccophilinae).

A new genus of laccophiline diving beetles, Laccomimus gen. n. , is here described on the basis of a large number of specimens from various collections formerly misidentified as members of the Neotropical genus Laccodytes Régimbart, 1895. Except for similar size, however, the new genus is not closely related to Laccodytes. Instead, it seems to be sister to the Oriental genus Laccosternus Brancucci, 1983, both sharing a similar body size and shape, characters of the female genital structures, and shape of the prosternal process. Twelve species are recognised within Laccomimus, all new to science except Laccomimus pumilio (LeConte, 1878) comb. n. , the type species. The new species are: Laccomimus alvarengi sp. n. , L. amazonas sp. n. , L. bolivari sp. n. , L. bordoni sp. n. , L. distinctus sp. n. , L. improvidus sp. n. , L. malkini sp. n. , L. spangleri sp. n. , L. spinosus sp. n. , L. variegatus sp. n. , L. youngi sp. n. The distribution of the new genus includes most of the Neotropics, with one species, L. pumilio, reaching Florida, USA. Each taxon is described and illustrated and a key for their identification is provided. Laccomimus is a widespread and relatively common genus in tropical America, the species of which have a wide distributional range, except for a few confined to more restricted areas. In spite of this, Laccomimus is a very uniform genus in body shape, size and colouration, and in most cases identification of the species is possible only after examination of the male genitalia. A key to distinguish genera of the tribe Laccophilini is also presented.
Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1)

Methylation of cytosine in DNA plays a crucial role in development through inheritable gene silencing. The DNA methyltransferase Dnmt1 is responsible for the propagation of methylation patterns to the next generation via its preferential methylation of hemimethylated CpG sites in the genome; however, how Dnmt1 maintains methylation patterns is not fully understood. Here we report the crystal structure of the large fragment (291–1620) of mouse Dnmt1 and its complexes with cofactor S-adenosyl-L-methionine and its product S-adenosyl-L-homocystein. Notably, in the absence of DNA, the N-terminal domain responsible for targeting Dnmt1 to replication foci is inserted into the DNA-binding pocket, indicating that this domain must be removed for methylation to occur. Upon binding of S-adenosyl-L-methionine, the catalytic cysteine residue undergoes a conformation transition to a catalytically competent position. For the recognition of hemimethylated DNA, Dnmt1 is expected to utilize a target recognition domain that overhangs the putative DNA-binding pocket. Taking into considerations the recent report of a shorter fragment structure of Dnmt1 that the CXXC motif positions itself in the catalytic pocket and prevents aberrant de novo methylation, we propose that maintenance methylation is a multistep process accompanied by structural changes.
Serial positron emission tomographic findings in an atypical presentation of fatal familial insomnia.

BACKGROUND Genetic analyses of fatal familial insomnia, a prion disease, disclose a broader range of symptoms than previously described. Although insomnia and dysautonomia have been described as hallmarks of the disease, there is substantial variability in clinical presentation. OBJECTIVE To evaluate serial fluorodeoxyglucose positron emission tomographic and electroencephalographic findings in atypical fatal familial insomnia without clinical insomnia. PATIENT A 63-year-old man who had a history of gait ataxia developed rapidly progressive dementia with mild dysautonomic features. Genetic investigation confirmed diagnosis of fatal familial insomnia (D178N mutation of the prion protein gene and Val/Met polymorphism on position 129 of the mutated allele) with typical neuropathologic findings. RESULTS Clinical signs were not specific. An electroencephalogram showed scanty triphasiclike elements and general slowing. We found thalamic hypometabolism in positron emission tomographic scans to be present in a very early stage with progressive deterioration, and patchy cortical alterations showing progression over 6 months. CONCLUSIONS In the absence of clear clinical signs, an electroencephalogram was of major diagnostic value, although its specificity in fatal familial insomnia is under debate. Selective thalamic hypometabolism seems to be an early marker in fatal familial insomnia, while cortical changes vary with clinical presentation and stage.
Solution structure and dynamics of the complex between cytochrome c and cytochrome c peroxidase determined by paramagnetic NMR

The physiological complex of yeast cytochrome c peroxidase and iso-1-cytochrome c is a paradigm for biological electron transfer. Using paramagnetic NMR spectroscopy, we have determined the conformation of the protein complex in solution, which is shown to be very similar to that observed in the crystal structure [Pelletier H, Kraut J (1992) Science 258:1748–1755]. Our results support the view that this transient electron transfer complex is dynamic. The solution structure represents the dominant protein–protein orientation, which, according to our estimates, is occupied for >70% of the lifetime of the complex, with the rest of the time spent in the dynamic encounter state. Based on the observed paramagnetic effects, we have delineated the conformational space sampled by the protein molecules during the dynamic part of the interaction, providing experimental support for the theoretical predictions of the classical Brownian dynamics study [Northrup SH, Boles JO, Reynolds JCL (1988) Science 241:67–70]. Our findings corroborate the dynamic behavior of this complex and offer an insight into the mechanism of the protein complex formation in solution.
Enhanced Stimulation of Diacylglycerol and Lipid Synthesis by Insulin in Denervated Muscle: Altered Protein Kinase C Activity and Possible Link to Insulin Resistance

Denervated muscle is generally regarded as insulin resistant because the ability of insulin to stimulate glucose transport and glycogen synthesis is impaired. Previous studies indicate that insulin resistance in these muscles is likely due to a defect at a postreceptor site in the signaling pathway. Because glucose transport into cells has been reported to be linked to changes in diacylglycerol (DAG) and protein kinase C (PKC), we investigated the effect of denervation on the content and synthesis of DAG and the activity and distribution of PKC in the soleus muscle. The DAG content in muscles denervated for 24 h was 40% > in control muscles. This was associated with a two- to threefold increase in the percentage of total PKC activity that was membrane associated, with no significant change in total PKC activity, suggesting an increase in PKC activity in vivo. Studies of glucose disposition confirmed that the stimulation of glycogen synthesis by insulin and, to a lesser extent, 2-deoxyglucose uptake were impaired by denervation. However, the stimulation by insulin of glucose incorporation into DAG and other lipids was two- to threefold greater in denervated than in control muscles, and conversion of glucose to lactate and pyruvate and glucose oxidation to CO2 were unchanged. The results reveal a dichotomy in the effects of denervation on various actions of insulin, with both insulin resistance and hyperresponsiveness occurring in different pathways of glucose metabolism. They also reveal a potential mechanism for the elevation of muscle DAG after denervation. The results do not support a direct link between DAG-PKC and glucose transport. Based on these findings, a working hypothesis that links enhanced DAG-PKC signaling to insulin resistance is proposed.
What are the Pathways through which Poverty is Perpetuated across Generations? Unlocking Possible Evidence for the Mexican Case 1

This article presents a compilation of literature about the process of inter-generational transmission of poverty. The article also addresses the possibilities of developing a study with evidence for the Mexican case. The first section of the article de-constructs the term intergenerational transmission of poverty. The second section reviews literature that allows us to understand the evolution of the topic, the theoretical underpinnings, and the evidence of the processes behind the transmission of poverty from one generation to another. The third section explores ways of finding possible evidence for Mexico. The article concludes that the growing interest in the country for understanding the perpetuation of poverty across generations is accompanied by slow—but solid—tools that would allow an empirical examination of the topic in the near future.
Financial Inclusion and Welfare in Post-Apartheid South Africa

The socioeconomic transformation process in post-apartheid South Africa has generated research on a wide range of economic issues, in particular, inequality and poverty. Surprisingly, there is limited empirical analysis on financial inclusion. This paper fills this void in the literature by answering two questions: (i) Does financial inclusion improve welfare? (ii) Is the benefit from using formal financial services greater than from using non-formal financial services? The paper uses a unique cross-sectional dataset on use of financial products over the period 2006–2011. Two measures of welfare are constructed – a well-being index and a wealth index. The sample is divided into users of formal financial services and users of non-formal financial services. The focus is on the differences in the welfare of the two groups. This difference in welfare is then decomposed through the Recentered Influence Function (RIF) approach. Finally, an OLS regression of the recentered welfare is estimated across quantiles for each group. Results show that: (i) overall, using formal financial products is associated with higher welfare; (ii) regardless of the measure of welfare used, the results are qualitatively similar: the wealth index picks up differences in the top quantiles, while the well-being index picks the differences in the lower quantiles; (iii) welfare disparities are accounted for by the unexplained factors related to income and education; and (iv) there are welfare gains from using non-formal credit and insurance products for individuals in the lower quantiles. The results suggest that the pursuit of financial inclusion should be complemented with policies that improve education and incomes, especially for the marginalised. Key words:Financial Inclusion; Recentered Influence Function; South Africa
Decreased polycystin 2 expression alters calcium-contraction coupling and changes β-adrenergic signaling pathways

Significance The main cause of death in autosomal-dominant polycystic kidney disease (ADPKD) patients is cardiac-related. However, the reasons why remain unclear. We show that mice lacking one copy of polycystin 2, a protein mutated in ADPKD, have altered calcium signaling and desensitized calcium-contraction coupling in cardiomyocytes. We also show that decreased polycystin 2 levels affect cardiac function by altering responses to adrenergic stimulus. We propose that altering polycystin levels in the heart directly contributes to remodeling of the heart in patients with ADPKD in the absence of renal failure or high blood pressure. Cardiac disorders are the main cause of mortality in autosomal-dominant polycystic kidney disease (ADPKD). However, how mutated polycystins predispose patients with ADPKD to cardiac pathologies before development of renal dysfunction is unknown. We investigate the effect of decreased levels of polycystin 2 (PC2), a calcium channel that interacts with the ryanodine receptor, on myocardial function. We hypothesize that heterozygous PC2 mice (Pkd2+/−) undergo cardiac remodeling as a result of changes in calcium handling, separate from renal complications. We found that Pkd2+/− cardiomyocytes have altered calcium handling, independent of desensitized calcium-contraction coupling. Paradoxically, in Pkd2+/− mice, protein kinase A (PKA) phosphorylation of phospholamban (PLB) was decreased, whereas PKA phosphorylation of troponin I was increased, explaining the decoupling between calcium signaling and contractility. In silico modeling supported this relationship. Echocardiography measurements showed that Pkd2+/− mice have increased left ventricular ejection fraction after stimulation with isoproterenol (ISO), a β-adrenergic receptor (βAR) agonist. Blockers of βAR-1 and βAR-2 inhibited the ISO response in Pkd2+/− mice, suggesting that the dephosphorylated state of PLB is primarily by βAR-2 signaling. Importantly, the Pkd2+/− mice were normotensive and had no evidence of renal cysts. Our results showed that decreased PC2 levels shifted the βAR pathway balance and changed expression of calcium handling proteins, which resulted in altered cardiac contractility. We propose that PC2 levels in the heart may directly contribute to cardiac remodeling in patients with ADPKD in the absence of renal dysfunction.
Clinical failures associated with rpoB mutations in phenotypically occult multidrug-resistant Mycobacterium tuberculosis.

SETTING Recently, Mycobacterium tuberculosis isolates have been described that test phenotypically susceptible to rifampicin (RMP) yet harbour genotypic rpoB mutations. OBJECTIVE 1) To investigate the impact of such mutations on clinical outcomes among RMP-susceptible isolates, and 2) to determine the prevalence of rpoB mutations among isoniazid (INH) monoresistant isolates at our laboratory and to describe the association between the presence of these mutations and clinical outcomes. METHODS M. tuberculosis isolates were screened for mutations in the rpoB gene using the Cepheid Gene-Xpert® MTB/RIF assay. Clinical correlation was made by reviewing patient case notes. RESULTS Isolates from 94 patients were found to have INH-resistant, RMP-susceptible profiles. Clinical information was available for 52 patients, including three whose isolates had rpoB mutations. All three of these patients had treatment failures, compared to two of 49 patients whose isolates did not have rpoB mutations (P = 0.0005). DISCUSSION We demonstrate a significant association between the presence of rpoB gene mutations that are not detected at the current RMP critical concentration and treatment failure. We suggest that a review of the current RMP critical concentration is warranted to ensure that RMP is not used inappropriately for the treatment of phenotypically occult multidrug-resistant tuberculosis.
[Cisplatin induces drug resistance in human esophageal squamous carcinoma cell line EC109 by decreasing CTR1 protein expression].

OBJECTIVE To investigate the mechanism of the development of cisplatin resistance in a human esophageal squamous carcinoma cell line. METHODS The cytotoxicity of cisplatin in the cisplatin-resistant resistant cell line EC109/CDDP and its parental cell line EC109 was measured by MTT assay. Whole-cell cisplatin accumulation and Pt-DNA adduct formation were determined by inductively coupled plasma mass spectrometry (ICP-MS). Western blotting was used to investigate the protein expression of full length PARP, cleaved PARP, and copper transporter 1 (CTR1). RESULTS EC109/CDDP cells was more resistant to cisplatin-induced cytotoxicity and apoptosis than EC109 cells. Compared with EC109 cells, EC109/CDDP cells exhibited less cisplatin accumulation and Pt-DNA adduct formation with also decreased CTR1 protein expression. CONCLUSION Cisplatin induces drug resistant phenotype by decreasing the protein level of CTR1, which controls cell accumulation and cytotoxic effect of cisplatin.
FERTILITY AFTER CHILDBIRTH: ADEQUACY OF POST‐PARTUM LUTEAL PHASES

Normal ranges of urinary pregnanediol and total urinary oestrogen were determined from weekly estimations in twenty‐seven cycles from seven normally menstruating control women and compared with the levels in the cycles of twenty‐seven breast feeding and ten bottle feeding mothers. During lactation, the luteal phase pregnanediol levels were within normal limits in thirteen of forty‐nine (27%) cycles, the remainder of the luteal phases being deficient (31%) or absent (42%). The proportion of normal luteal phases remained low during first cycles after lactation in six of twenty‐three (26%) but rose to twenty‐four of thirty‐one (77%) in subsequent cycles. In bottle feeding mothers, the luteal phases of first post‐partum cycles were deficient in two often (20%) and absent in eight of ten (80%). In second post‐partum cycles, the majority of luteal phases were deficient (eight often, 80%) and it was not until third post‐partum cycles that seven of eight (88%) had luteal phase pregnanediol levels in the normal range. Cycles during lactation and first cycles after lactation had significantly lower mean urinary pregnanediol and total urinary oestrogen levels than both the control cycles and the later cycles after lactation. Similarly, first post‐partum cycles in bottle feeders had lower urinary pregnanediol and total urinary oestrogen levels than controls. This study shows an increased frequency of abnormal luteal phases during the early post‐partum menstrual cycles of both breast and bottle feeding mothers which may be associated with defective development of the follicle.