Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid Methods for High-Throughput Detection of Sulfoxides

ABSTRACT Enantiopure sulfoxides are prevalent in drugs and are useful chiral auxiliaries in organic synthesis. The biocatalytic enantioselective oxidation of prochiral sulfides is a direct and economical approach for the synthesis of optically pure sulfoxides. The selection of suitable biocatalysts requires rapid and reliable high-throughput screening methods. Here we present four different methods for detecting sulfoxides produced via whole-cell biocatalysis, three of which were exploited for high-throughput screening. Fluorescence detection based on the acid activation of omeprazole was utilized for high-throughput screening of mutant libraries of toluene monooxygenases, but no active variants have been discovered yet. The second method is based on the reduction of sulfoxides to sulfides, with the coupled release and measurement of iodine. The availability of solvent-resistant microtiter plates enabled us to modify the method to a high-throughput format. The third method, selective inhibition of horse liver alcohol dehydrogenase, was used to rapidly screen highly active and/or enantioselective variants at position V106 of toluene ortho-monooxygenase in a saturation mutagenesis library, using methyl-p-tolyl sulfide as the substrate. A success rate of 89% (i.e., 11% false positives) was obtained, and two new mutants were selected. The fourth method is based on the colorimetric detection of adrenochrome, a back-titration procedure which measures the concentration of the periodate-sensitive sulfide. Due to low sensitivity during whole-cell screening, this method was found to be useful only for determining the presence or absence of sulfoxide in the reaction. The methods described in the present work are simple and inexpensive and do not require special equipment.
Linkage of Organic Anion Transporter-1 to Metabolic Pathways through Integrated “Omics”-driven Network and Functional Analysis*

The main kidney transporter of many commonly prescribed drugs (e.g. penicillins, diuretics, antivirals, methotrexate, and non-steroidal anti-inflammatory drugs) is organic anion transporter-1 (OAT1), originally identified as NKT (Lopez-Nieto, C. E., You, G., Bush, K. T., Barros, E. J., Beier, D. R., and Nigam, S. K. (1997) J. Biol. Chem. 272, 6471–6478). Targeted metabolomics in knockouts have shown that OAT1 mediates the secretion or reabsorption of many important metabolites, including intermediates in carbohydrate, fatty acid, and amino acid metabolism. This observation raises the possibility that OAT1 helps regulate broader metabolic activities. We therefore examined the potential roles of OAT1 in metabolic pathways using Recon 1, a functionally tested genome-scale reconstruction of human metabolism. A computational approach was used to analyze in vivo metabolomic as well as transcriptomic data from wild-type and OAT1 knock-out animals, resulting in the implication of several metabolic pathways, including the citric acid cycle, polyamine, and fatty acid metabolism. Validation by in vitro and ex vivo analysis using Xenopus oocyte, cell culture, and kidney tissue assays demonstrated interactions between OAT1 and key intermediates in these metabolic pathways, including previously unknown substrates, such as polyamines (e.g. spermine and spermidine). A genome-scale metabolic network reconstruction generated some experimentally supported predictions for metabolic pathways linked to OAT1-related transport. The data support the possibility that the SLC22 and other families of transporters, known to be expressed in many tissues and primarily known for drug and toxin clearance, are integral to a number of endogenous pathways and may be involved in a larger remote sensing and signaling system (Ahn, S. Y., and Nigam, S. K. (2009) Mol. Pharmacol. 76, 481–490, and Wu, W. , Dnyanmote, A. V. , and Nigam, S. K. (2011) Mol. Pharmacol. 79, 795–805). Drugs may alter metabolism by competing for OAT1 binding of metabolites.
Femoral and axillary ultrasound blood flow during exercise: a methodological study.

PURPOSE To use Doppler ultrasound 1) to assess the relationship between exercise intensity and changes in femoral and axillary artery diameter, 2) to determine whether volume blood flow (BF) measured during early recovery accurately reflects exercise BF, and 3) to assess the influence of artery caliber and/or site as well as exercise intensity on BF measurement reproducibility. METHODS Thirteen healthy subjects (mean age 25.9+/-7.7 yr) performed progressive and maximal leg-extension (LE) and elbow-flexion (EF) exercises in the supine position. The duration of each stage was 150 s, followed by a 30-s recovery period. Arterial diameter and blood flow velocity were recorded simultaneously and continuously during the last 30 s of exercise as well as 30 s into recovery. RESULTS Arterial dilation was 3.5 and 6.5% at maximal effort in femoral and axillary arteries, respectively. A significant increase was observed for both arteries from workload 2 to peak exercise when arterial cross-sectional area was calculated. Blood flow velocity during the recovery period was significantly different from end-exercise values, depending on time and workload. The coefficients of variation of BF measurement during exercise were 7.1-12.1% and 6.4-9.5% in LE and EF, respectively. CONCLUSION This study showed that BF measurement with Doppler ultrasound during exercise is reproducible but requires measurement of arterial diameter at each workload. Measurements performed immediately after exercise cannot be used as a surrogate for blood flow velocity during exercise.
A structural polypeptide of the baculovirus Autographa californica nuclear polyhedrosis virus contains O-linked N-acetylglucosamine

A structural glycopeptide, gp41, derived from the occluded virus of the baculovirus Autographa californica nuclear polyhedrosis virus was characterized. The peptide specifically bound wheat germ agglutinin but was not recognized by a panel of seven other lectins. Reactivity with wheat germ agglutinin was eliminated by treatment of gp41 with beta-N-acetylglucosaminidase, indicating that N-acetylglucosamine (GlcNAc) was present as terminal residues. gp41 was efficiently galactosylated by galactosyltransferase only in the presence of Nonidet P-40, suggesting that GlcNAc residues are not exposed on the surface of the virion. Metabolic labelling of gp41 with [3H]GlcNAc occurred in the presence of tunicamycin. The carbohydrate was released by alkaline borohydride treatment and comigrated with N-acetylglucosaminitol in descending paper chromatography. The data indicate that gp41 contains single residues of GlcNAc O glycosidically linked to the polypeptide chain. Evidence suggesting that gp41 is located in the region between the envelope membrane and the capsid (defined here as the tegument) of the occluded virus is also presented.
Time Course of Seroconversion by HerpeSelect ELISA After Acquisition of Genital Herpes Simplex Virus Type 1 (HSV-1) or HSV-2

Background HerpeSelect HSV-1 and HSV-2 ELISAs are glycoprotein G–based, type-specific antibody detection tests that are approved by the US Food and Drug Administration for diagnosis of genital herpes. Goal The goal was to determine seroconversion times by means of HerpeSelect ELISAs. Study Design Four-hundred thirteen sera from 113 patients with recently acquired genital herpes were tested by HerpeSelect ELISAs and Western blot (WB). Thirty-one patients had primary genital HSV-1 (group 1), 56 had primary HSV-2 (group 2), and 26 had prior HSV-1 antibodies and newly acquired HSV-2 (group 3). Results Median interval from onset of symptoms to seroconversion was 25 days, as determined by HerpeSelect HSV-1, versus 33 days by WB for group 1; 21 days by HerpeSelect HSV-2 versus 40 days by WB (group 2;P = 0.0005); and 23 days by HerpeSelect HSV-2 ELISA versus 47 days by WB (group 3;P = 0.02). In long-term follow-up, transient reversion to HerpeSelect negativity occurred in 3 of 31 HSV-1-infected subjects (10%) and in 2 of 82 HSV-2-infected subjects (2%). Conclusion Seroconversion to HSV-2 was determined faster by HerpeSelect than by WB.
Peak flow variability in the SAPALDIA study and its validity in screening for asthma-related conditions. The SPALDIA Team.

We used 3-wk peak expiratory flow (PEF) measurements (twice daily) made in the diary study of the population-based Swiss Study on Air Pollution and Lung Disease in Adults to describe PEF-variability (PEF(var)) (amplitude as a percent of the mean, PEF [i.e., difference between morning and evening values divided by the mean]) in the study population and in five subgroups (physician-diagnosed asthma; current asthma, or physician-diagnosed asthma plus asthma attacks and/or medication; history of wheezing without a cold; hyperreactive; and nonsymptomatic). We assessed the performance of PEF(var) as a potential tool with which to screen for asthma. Alternatively, subjects with a PEF(var) of >/= 20%, >/= 30%, and >/= 50% on at least 2 d were considered to have high variability. The analyses were conducted for subgroups with different pretest probabilities for asthma-related conditions. The median PEF(var) was 4.5%. Among asthmatic subjects, women had nonsignificantly higher PEF(var) values than did men. In all other groups, women had significantly lower PEF(var). Both in the entire population and in subgroups with a higher pretest probability for asthma-related conditions, screening performance of PEF was limited. A PEF(var) of >/= 20% on at least 2 d detected current asthma with a sensitivity of 36% (specificity = 90%; positive predictive value = 16.4%). Results were better among subjects with a history of wheezing without colds (sensitivity = 40.4%; specificity = 83.6%; positive predictive value = 45.2%). PEF(var), a useful measure both clinically and in epidemiology, is of limited value when unselected populations are screened for asthma-related conditions, since the overlap of PEF(var) distributions across subgroups is large.
Cognitive Performance of Morbidly Obese Patients Seeking Bariatric Surgery

Bariatric surgery is efficacious for the treatment of severe obesity; however, little empirical research exists describing the demographic, psychosocial, and cognitive characteristics of patients presenting for the surgery. One hundred and sixty-nine morbidly obese patients seeking bariatric surgery underwent a presurgical psychological assessment, including cognitive testing. Morbidly obese individuals seeking bariatric surgery were similar in education, income status, and IQ compared with normative data. IQ was average, did not correlate with body mass index, and reflected a normal distribution. As a group, bariatric surgery patients endorsed minimal levels of depression and low levels of psychopathology. Obese individuals did demonstrate specific cognitive deficits on tests of executive function (e.g., problem solving and planning) when compared with normative data. This data suggests that bariatric surgery patients differ very little from other surgical populations on most demographic and psychosocial variables. The data does provide evidence for specific cognitive deficits in the area of executive functions at baseline in morbidly obese adults seeking bariatric surgery.
A Two-Part Approach to Examine the Effects of Theacrine (TeaCrine®) Supplementation on Oxygen Consumption, Hemodynamic Responses, and Subjective Measures of Cognitive and Psychometric Parameters

ABSTRACT Theacrine (1,3,7,9-tetramethyluric acid) is a naturally occurring purine alkaloid, present in Camellia assamica variety kucha tea. Using a two-part approach in humans, the impact of theacrine (TeaCrine®, TC) was used to examine subjective dose–response, daily changes in cognitive and psychometric parameters, and changes in gas exchange and vital signs. All indicators were chosen to better ascertain the previously reported animal and human outcomes involving theacrine administration. Part 1 was a randomized, open-label, dose–response investigation in nine healthy participants whereby three participants ingested 400 mg TC per day and six participants ingested 200 mg/day. Participants recorded subjective changes in cognitive, psychometric, and exercise attributes using 150-mm anchored visual analog scale (VAS) before, and 1, 4, and 6 hours after ingestion every day for 7 consecutive days. Part 2 was a randomized, double-blind, placebo-controlled, crossover investigation in 15 healthy subjects in which all participants ingested a single 200 mg dose of TC or Placebo (PLA). Anchored VAS questionnaires were used to detect subjective changes in various aspects of physical and mental energy along with changes in gas exchange and hemodynamic parameters before, and 1, 2, and 3 hours after acute ingestion. Energy, focus, and concentration increased from baseline values in both doses with no dose-response effect. VAS responses in the 200 mg for willingness to exercise, anxiety, motivation to train and libido increased across the measurement period while no such change was seen with the 400 mg dose. After consuming a single 200 mg dose, significant group × time interaction effects were seen for energy, fatigue, and concentration. No changes in resting heart rate, gas exchange, systemic hemodynamics or side effect profiles were noted.
Identification of a novel Gsp‐related pathway required for secretion of the manganese‐oxidizing factor of Pseudomonas putida strain GB‐1

The manganese‐oxidizing factor of Pseudomonas putida strain GB‐1 is associated with the outer membrane. One of the systems of protein transport across the outer membrane is the general secretory pathway (Gsp). The gsp genes are called xcp in Pseudomonas species. In a previous study, it was shown that mutation of the prepilin peptidase XcpA and of a homologue of the pseudopilin XcpT inhibited transport of the factor. In the present study, we describe the genomic region flanking the xcpT homologue (designated xcmT1). We show that xcmT1 is part of a two‐gene operon that includes an xcpS homologue (designated xcmS). No other xcp‐like genes are present in the regions flanking the xcmT1/xcmS cluster. We also characterized the site of transposon insertion of another transport mutant of P. putida GB‐1. This insertion appeared to be located in a gene (designated xcmX) possibly encoding another pseudopilin‐related protein. This xcmX is clustered with two other xcpT‐related genes (designated xcmT2 and xcmT3) on one side and homologues of three csg genes (designated csmE, csmF and csmG) on the other side. The csg genes are involved in production of aggregative fibres in Escherichia coli and Salmonella typhimurium. A search for XcmX homologues revealed that the recently published genome of Ralstonia solanacearum and the unannotated genome of P. putida KT2440 contain comparable gene clusters with xcmX and xcp homologues that are different from the well‐described ‘regular’xcp/gsp clusters. They do contain xcpR and xcpQ homologues but, for example, homologues of xcpP, Y and Z are lacking. The results suggest a novel Xcp‐related system for the transport of manganese‐oxidizing enzymes to the cell surface.
Analysis of D2D Underlaid Cellular Networks: SIR Meta Distribution and Mean Local Delay

We study the performance of device-to-device (D2D) communication underlaying cellular wireless network in terms of the meta distribution of the signal-to-interference ratio (SIR), which is the distribution of the conditional SIR distribution given the locations of the wireless nodes. Modeling D2D transmitters and base stations as Poisson point processes (PPPs), moments of the conditional SIR distribution are derived in order to calculate analytical expressions for the meta distribution and the mean local delay of the typical D2D receiver and cellular downlink user. It turns out that for D2D users, the total interference from the D2D interferers and base stations is equal in distribution to that of a single PPP, while for downlink users, the effect of the interference from the D2D network is more complicated. We also derive the region of transmit probabilities for the D2D users and base stations that result in a finite mean local delay and give a simple inner bound on that region. Finally, the impact of increasing the base station density on the mean local delay, the meta distribution, and the density of users reliably served is investigated with numerical results.
Dissociable patterns of brain activity for mentalizing about known others: a role for attachment

Abstract The human brain tracks dynamic changes within the social environment, forming and updating representations of individuals in our social milieu. This mechanism of social navigation builds an increasingly complex map of persons with whom we are familiar and form attachments to guide adaptive social behaviors. We examined the neural representation of known others along a continuum of attachment using fMRI. Heterosexual adults (N = 29, 16 females), in romantic relationships for more than 2 years, made trait judgments for a romantic partner, parent, close friend, familiar acquaintance and self-during scanning. Multivariate analysis, partial least squares, was used to identify whole-brain patterns of brain activation associated with trait judgments of known others across a continuum of attachment. Across conditions, trait judgments engaged the default network and lateral prefrontal cortex. Judgments about oneself and a partner were associated with a common activation pattern encompassing anterior and middle cingulate, posterior superior temporal sulcus, as well as anterior insula. Parent and close friend judgments engaged medial and anterior temporal lobe regions. These results provide novel evidence that mentalizing about known familiar others results in differential brain activity. We provide initial evidence that the representation of adult attachment is a distinguishing feature of these differences.
Jade-1S phosphorylation induced by CK1α contributes to cell cycle progression

ABSTRACT The PHD zinc finger protein Jade-1S is a component of the HBO1 histone acetyltransferase complex and binds chromatin in a cell cycle-dependent manner. Jade-1S also acts as an E3 ubiquitin ligase for the canonical Wnt effector protein β-catenin and is influenced by CK1α-mediated phosphorylation. To further elucidate the functional impact of this phosphorylation, we used a stable, low-level expression system to express either wild-type or mutant Jade-1S lacking the N-terminal CK1α phosphorylation motif. Interactome analyses revealed that the Jade-1S mutant unable to be phosphorylated by CK1α has an increased binding affinity to proteins involved in chromatin remodelling, histone deacetylation, transcriptional repression, and ribosome biogenesis. Interestingly, cells expressing the mutant displayed an elongated cell shape and a delay in cell cycle progression. Finally, phosphoproteomic analyses allowed identification of a Jade-1S site phosphorylated in the presence of CK1α but closely resembling a PLK1 phosphorylation motif. Our data suggest that Jade-1S phosphorylation at an N-terminal CK1α motif creates a PLK1 phospho-binding domain. We propose CK1α phosphorylation of Jade 1S to serve as a molecular switch, turning off chromatin remodelling functions of Jade-1S and allowing timely cell cycle progression. As Jade-1S protein expression in the kidney is altered upon renal injury, this could contribute to understanding mechanisms underlying epithelial injury repair.
LTP of GABAergic synapses in the ventral tegmental area and beyond

One of the mechanisms by which the experience‐dependent reorganization of neural circuitry can occur is through changes in synaptic strength. Almost every excitatory synapse in the mammalian brain exhibits LTP (long‐term potentiation) or LTD (long‐term depression), two cellular mechanisms of synaptic plasticity. However, LTP and LTD have been reported much more rarely at fast inhibitory GABAA receptor synapses. Our recent study suggests that in vivo morphine initiates a long‐lasting alteration of GABAergic synapses in the ventral tegmental area (VTA) by blocking the mechanisms required for LTP of GABAergic synapses. Here we put this work into the context of other examples of synaptic plasticity at GABAergic synapses.
Elderhood in ethnic conflict management in Rongai, Nakuru County, Kenya; 1992-2015

This study investigated elderhood in ethnic conflict management in Kenya‟s Rongai Sub-county from 1992 to 2015. It is to be appreciated that ethnic conflict management results in peace which in turn creates a fertile environment for achievement of sustainable development. Western and contemporary conflict resolution mechanisms, which have been in use for decades, have not yielded the desired results and rather than solely relying on their legal and lengthy judicial processes, indigenous mechanisms have been sought. One such mechanism is the institution of elders which has become instrumental in addressing the prevailing challenges of ethnic based violence. This study specifically investigated the nature, origin and causes of ethnic conflicts, examined the institution of elderhood, and interrogated the roles of elders in ethnic conflicts management in Rongai Sub-county. The study was based on the following premises: Land was the major cause of ethnic conflicts in Rongai Sub-county, elderhood institutions commanded respect among majority of ethnic groups in Rongai Sub-county and that the institution of elders played a significant role in ethnic conflict management in Rongai Sub-county. The study was guided by Protracted Social Conflict Theory and Conflict Transformation Theory. The study adopted descriptive research design. The target population was the people of Rongai Sub-county. The sample size was obtained using purposive and snowballing sampling techniques. Both primary and secondary data was collected. The primary data was collected using indepth interviews and focus group discussions while secondary data was obtained from both published and unpublished records, magazines and books. The data collected was analyzed using thematic analysis where categories of responses for each objective from the respondents were identified, classified and combined into themes. The data was then interpreted and presented based on these categories and themes. This study has three major findings. First, the ethnic conflicts in Rongai Sub-county were mainly of violent nature, originated from the reintroduction of multi-party politics in Kenya in early 1990s and were caused mainly by land and political issues. Secondly, the institution of elderhood was strong in Rongai Sub-county and commanded respect in the management of ethnic conflicts. Thirdly, the elders were the lead actors in ethnic conflicts management in Rongai Sub-county and played key roles that were aimed at achieving peaceful co-existence among ethnic groups. The study, therefore, recommends that the institution of elderhood be supported by the government and given a leading role in ethnic conflicts management. Secondly, the underlying cause of ethnic conflicts be identified and resolved proactively. Thirdly, ways should be found to weed out the culture of intolerance and impunity among ethnic communities in Rongai Sub-county.