Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro reconstitution of the myxochelin biosynthetic machinery of Stigmatella aurantiaca Sg a15: Biochemical characterization of a reductive release mechanism from nonribosomal peptide synthetases

Microorganisms produce iron-chelating compounds to sequester the iron essential for growth from the environment. Many of these compounds are biosynthesized by nonribosomal peptide synthetases, some in cooperation with polyketide synthases. Myxochelins are produced by the myxobacterium Stigmatella aurantiaca Sg a15, and the corresponding gene cluster was cloned recently. We have undertaken to express heterologously the myxochelin biosynthetic machinery in Escherichia coli. To activate the involved proteins posttranslationally, they were coexpressed with the phosphopantetheinyltransferase MtaA from the myxothiazol biosynthetic gene cluster. Phosphopantetheinylation of the carrier proteins could be verified by protein mass analysis. Six active domains in proteins MxcE, MxcF, and MxcG are capable of assembling myxochelin from ATP, NAD(P)H, lysine, and 2,3-dihydroxybenzoic acid in vitro. This fact demonstrates that the condensation domain of MxcG performs two condensation reactions, creating the aryl-capped α-amide and the aryl-capped γ-amide of the molecule. A previously unknown type of reductive release is performed by the reduction domain of MxcG, which alternatively uses NADPH and NADH to set free the peptidyl-carrier protein-bound thioester as an aldehyde and further reduces it to the alcohol structure that can be found in myxochelin A. This type of reductive release seems to be a general mechanism in polyketide and nonribosomal peptide biosynthesis, because several systems with C-terminal similarity to the reductase domain of MxcG can be found in the databases. Alternatively, the aldehyde can be transaminated, giving rise to a terminal amine.
Pattern of spread to the lateral neck in metastatic well-differentiated thyroid cancer: a systematic review and meta-analysis.

BACKGROUND There remains controversy surrounding the extent of lateral neck dissection required in patients with papillary thyroid cancer (PTC) and suspicious or confirmed metastatic lateral neck lymphadenopathy. The evidence for this clinical dilemma has never been reviewed systematically nor has there been an attempt to meta-analyze the data by lymph node levels to better characterize the pattern of spread. METHODS This meta-analysis used MEDLINE and EMBASE including all cohort studies reporting the pattern of lateral neck disease in patients who underwent a neck dissection for clinically, radiographically, or cytologically suspicious or confirmed metastatic lymphadenopathy for PTC. Our main outcome was the number of patients with positive involvement at a given level as a percentage of the cohort of patients with positive lateral neck disease, each level being measured separately. RESULTS Eighteen studies with a total of 1145 patients and 1298 neck dissections were included in our meta-analysis. Levels IIa and IIb had disease in 53.1% [95% confidence interval (CI) 46.6-59.5%] and 15.5% [CI 8.2-27.2%], respectively. Studies that did not distinguish between level IIa and IIb or in which both were collapsed into one category showed a total level II involvement of 53.4% [CI 49.7-57.1%]. Level III and level IV were involved in 70.5% [CI 67.0-73.9%] and 66.3% [CI 61.4-70.9%] of specimens. Studies that did not distinguish between level Va and Vb or in which both were collapsed into one category showed a total level V involvement of 25.3% [CI 20.0-31.5%]. Levels Va and Vb had positivity in 7.9% [CI 2.8-20.0%] and 21.5% [CI 7.7-47.6%], respectively, but had only three studies that could be meta-analyzed. CONCLUSIONS This systematic review of the literature and meta-analysis of the pattern of spread indicates significant rates of lymph node metastasis to all lateral neck levels in patients with PTC with regional involvement. This evidence leads us to recommend a comprehensive selective neck dissection of levels IIa, IIb, III, IV, and Vb in patients with lateral neck disease from PTC. The evidence for level Va is lacking, as most studies did not distinguish between levels Va and Vb, and the border between the two levels was inconsistent. Future studies will need to address these sublevels separately.
Enemas during labour.

BACKGROUND Although the use of enemas during labour usually reflects the preference of the attending healthcare provider, enemas may cause discomfort for women. OBJECTIVES To assess the effects of enemas applied during the first stage of labour on maternal and neonatal outcomes. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 May 2012), the Cochrane Central Register of Controlled Trials and Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2012, Issue 5), PubMed (1966 to 17 May 2012), LILACS (17 May 2012), the Search Portal of the International Clinical Trials Registry Platform (ICTRP) (17 May 2012), Health Technology Assessment Program, UK (17 May 2012), Medical Research Council, UK (17 May 2012), The Wellcome Trust, UK (17 May 2012) and reference lists of retrieved articles. SELECTION CRITERIA Randomised controlled trials (RCTs) in which an enema was administered during the first stage of labour and which included assessment of possible neonatal or puerperal morbidity or mortality. DATA COLLECTION AND ANALYSIS Two review authors independently assessed studies for inclusion. MAIN RESULTS Four RCTs (1917 women) met the inclusion criteria. One study was judged as having a low risk of bias. In the meta-analysis we conducted of two trials, we found no significant difference in infection rates for puerperal women (two RCTs; 594 women; risk ratio (RR) 0.66, 95% confidence (CI) 0.42 to 1.04). No significant differences were found in neonatal umbilical infection rates (two RCTs; 592 women; RR 3.16, 95% CI 0.50 to 19.82; I² 0%. In addition, meta-analysis of two studies found that there were no significant differences in the degree of perineal tear between groups. Finally, meta-analysis of two trials found no significant differences in the mean duration of labour. AUTHORS' CONCLUSIONS The evidence provided by the four included RCTs shows that enemas do not have a significant beneficial effect on infection rates such as perineal wound infection or other neonatal infections and women's satisfaction. These findings speak against the routine use of enemas during labour, therefore, such practice should be discouraged.
Exploring mixed emotions and emotion-regulation strategies of students balancing higher education with employment

ABSTRACT Higher education participation rates are rising globally, and an increasing proportion of students are combining educational studies with paid employment. A plethora of research has focused on examining the nexus between higher education and employment, with outcomes largely geared towards investigating the negative effects of combining these roles. Limited scholarly attention has been directed towards understanding the emotional impact and effect on work–life balance when navigating the challenges associated with combining higher education and employment. This manuscript reports on 20 undergraduate student interviews from a higher education institution in Sri Lanka. Drawing from an emotion-regulation perspective, this research examines the ways in which students experience and manage emotions when combining higher education studies with employment. The Sri Lankan context provides an interesting case given the presence of rapid economic growth in the region, coupled with a rise in higher education involvement. The findings highlight that polarised mixed emotions are prevalent amongst a cohort of students who combine higher education with employment. Overall, the research supports further exploration of the emotional challenges of students balancing higher education and employment to effectively prepare students for the complexities of combining these roles.
Immigration and Social Mobility

Using Norwegian administrative data, we examine how exposure to immigration over the past decades has affected natives' relative prime age labor market outcomes by social class background. Social class is established on the basis of parents' earnings rank. By exploiting variation in immigration patterns over time across commuting zones, we find that immigration from low‐income countries has reduced social mobility and thus steepened the social gradient in natives' labor market outcomes, whereas immigration from high‐income countries has leveled it. Given the large inflow of immigrants from low-income countries to Norway since the early 1990s, this can explain a considerable part of the relative decline in economic performance among natives with lower class background, and also rationalize the apparent polarization of sentiments toward immigration.
Genetic vulnerabilities to prenatal alcohol exposure: Limb defects in sonic hedgehog and GLI2 heterozygous mice.

BACKGROUND Genetic factors influence the physical and neurobehavioral manifestations of prenatal alcohol exposure (PAE). Animal models allow the investigation of specific genes that confer vulnerability to, or protection from, birth defects associated with fetal alcohol spectrum disorders (FASDs). The objective of the present experiments was to determine if genetic alterations in the Sonic Hedgehog (Shh) signaling pathways affect the vulnerability to PAE-induced skeletal defects involving the forelimbs and/or hindlimbs. METHOD Wild-type C57BL/6J female mice were bred with males in which one copy of the Shh or Gli2 genes had been knocked out, to produce litters with both wild-type (+/+) and heterozygous (+/-) embryos. Alcohol doses (two injections of 2.9 g/kg, 4 hours apart) or vehicles were administered starting at gestational day (GD) 9.25, 9.5, or 9.75, a critical exposure time for inducing limb defects. Limb defects were examined at GD 17 using a dysmorphology scale based on abnormalities ranging from increased interdigital spacing to the deletion of multiple fingers and the ulna. RESULTS Alcohol treatment caused a high incidence of forelimb defects, particularly on the right side, that was higher in Shh+/- and Gli2+/- fetuses compared to wild-type fetuses. Dysmorphology scores were also significantly higher in the Shh+/- and Gli2+/- mice. CONCLUSIONS These results extend previous findings demonstrating enhanced sensitivity to PAE-induced craniofacial dysmorphology and support the hypothesis that genetic alterations in the Shh signaling pathway influences the vulnerability to alcohol-induced birth defects. Moreover, these results emphasize the importance of understanding the interactions between genes and prenatal exposure to alcohol or other teratogens. Birth Defects Research 109:860-865, 2017. © 2017 Wiley Periodicals, Inc.
A Comparison of Body Composition Across Two Phases of the Menstrual Cycle Utilizing Dual-Energy X-Ray Absorptiometry, Air Displacement Plethysmography, and Bioelectrical Impedance Analysis

The purpose of this investigation was to utilize several different technologies to compare body composition results across two phases of the menstrual cycle, and to investigate whether being on hormonal birth control or not has any effect on results. The secondary purpose was to determine if body satisfaction or perception of fluid retention differed across phases or between groups. A total of 39 females with a mean age of 26 ± 7 yrs were included in the study, 15 were on hormonal birth control (BC) and 24 were not (non-BC). Participants came into the lab for two trials: once while menstruating and another during the estimated pre-ovulation phase of the menstrual cycle. Demographic and body satisfaction questionnaires were completed prior to body composition testing. This testing included dual-energy x-ray absorptiometry, BOD POD®, and three separate bioelectrical impedance analyses. Participants completed the body satisfaction questionnaire and all body composition tests on each trial. No significant differences (P > 0.05) were found between body fat percentage or total body water estimates taken during menses and pre-ovulation for the BC or non-BC group. There was no significant difference (P > 0.05) in overall body satisfaction across the two phases for the non-BC group, though the BC group had significantly lower body satisfaction during menses (P < 0.01). Participants in both groups identified feeling more bloated during menses (P < 0.001). Results suggest that menses should not affect the reliability of body composition estimates regardless of whether or not females are on hormonal BC.
Physiological function of the Pseudomonas putida PpG6 (Pseudomonas oleovorans) alkane hydroxylase: monoterminal oxidation of alkanes and fatty acids

Pseudomonas putida PpG6 is able to utilize purified n-alkanes of six to ten carbon atoms for growth. It can also grow on the primary terminal oxidation products of these alkanes and on 1-dodecanol but not on the corresponding 2-ketones or 1,6-hexanediol, adipic acid, or pimelic acid. Revertible point mutants can be isolated which have simultaneously lost the ability to grow on all five n-alkane growth substrates but which can still grow on octanol or nonanol. An acetate-negative mutant defective in isocitrate lysase activity is unable to grow on even-numbered alkanes and fatty acids. Analysis of double mutants defective in acetate and propionate or in acetate and glutarate metabolism shows that alkane carbon is assimilated only via acetyl-coenzyme A and propionyl-coenzyme A. These results support the following conclusions: (i) The n-alkane growth specificity of P. putida PpG6 is due to the substrate specificity of whole-cell alkane hydroxylation; (ii) there is a single alkane hydroxylase enzyme complex; (iii) the physiological role of this complex is to initiate the monoterminal oxidation of alkane chains; and (iv) straight-chain fatty acids from butyric through nonanoic are degraded exclusively by beta-oxidation from the carboxyl end of the molecule.
Binding of Zinc Finger Protein Transcription Factor IIIA to Its Cognate DNA Sequence with Single UV Photoproducts at Specific Sites and Its Effect on DNA Repair*

The relationship between DNA repair efficiency at specific locations in the binding site of the nine-zinc finger protein transcription factor IIIA (TFIIIA) and binding of its individual zinc fingers was studied. Homogeneously damaged oligonucleotides, which contained a single cis-syn cyclobutane thymine dimer (CTD) at one of six different sites in the internal control region (ICR) of the 5 S rRNA gene to generate a series of damaged DNA substrates, were prepared by chemical synthesis. Binding of TFIIIA to the substrates was assayed by measurement of dissociation constants (Kd), dissociation rates (koff), and protein-DNA contacts. The results indicated that a single CTD in the ICR does not significantly affect the Kd of TFIIIA. In contrast, CTDs at positions +55 and +72 (from the transcription start site) in the ICR markedly enhanced koff of TFIIIA from the complex. In addition, CTDs in these two sites increased methylation of the N7 of guanines (by dimethyl sulfate) in the zinc finger contacts of the ICR-TFIIIA complex. Furthermore CTDs at +55 and +72 were more efficiently removed from the complex than CTDs at other sites in the ICR by Xenopus oocyte nuclear extracts. This suggests that repair of CTDs closely correlates with changes in the binding of individual zinc fingers of the ICR-TFIIIA complex. These results have implications for the mechanism of DNA damage recognition and repair in protein-DNA complexes.
The effects of old age and distraction on the assessment of prospective memory in a simulated naturalistic environment

ABSTRACT Background: The ability to remember to complete future intentions, prospective memory, often begins to fail in old age. The aim of the present study was to examine the sensitivity of a computer-based procedure using naturalistic stimuli to age-related increases in forgetting under conditions of high (increased visual and auditory noise) or low distraction. Methods: Participants were tested in a virtual shopping precinct constructed from linked photographs, sounds, and video segments. Groups of 32 older and younger persons completed two concurrent memory tasks while moving along the street. In one task, participants were given errands to complete with an accessible checklist, in the other, they were required to remember to respond to three different targets that appeared repeatedly. Results: The results confirmed previous findings that older adults have difficulty remembering future intentions, even on a self-paced task using naturalistic stimuli, and showed that this was accentuated in noisy environments. Conclusions: Older persons have particular difficulty remembering in noisy environments, and results from testing in the clinic may underestimate the practical memory problems experienced by older adults with mild cognitive impairments. The findings provide encouragement for the construction of computer-generated environments to measure functional deficits in cognition.
High intensity strength training improves strength and functional performance after stroke.

OBJECTIVE To evaluate the effects of a progressive resistance strength training program on changes in muscle strength, gait, and balance in older individuals 1 yr after stroke, seven individuals were recruited who were greater than 60-yr-old, 1 yr after stroke, living at home, and able to follow verbal commands. DESIGN Subjects participated in a 12-wk 2x per wk resistance training program at 70% of 1 repetition maximum. RESULTS Lower limb strength improved 68% on the affected side and 48% on the intact side during training, with the largest increases observed for hip extension (affected side: 88%, P < 0.01; intact side: 103%, P < 0.001). Repeated chair stand time decreased 21% (P < 0.02). Motor performance assessed by the Motor Assessment Scale improved 9% (P < 0.04) and static and dynamic balance (Berg balance scale) improved 12% (P < 0.004). Progressive resistance training in individuals 1 yr after stroke improves affected and intact side lower limb strength and was associated with gains in chair stand time, balance, and motor performance. CONCLUSIONS These results support the concept that strength training is an appropriate intervention to improve the quality of physical function in older community dwelling stroke survivors.
Coffee Consumption Could Affect the Activity of Some Liver Enzymes and Other Biochemical Parameters in Healthy Drinkers

Objective: To investigate the effect of coffee consumption on some liver function indices in adult male and female Nigerians. Subjects and Methods: Thirty apparently healthy subjects, consisting of 18 men and 12 women, were made to consume 2 g of coffee daily for a total of 30 days. Activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and plasma concentrations of total and conjugated bilirubin, total protein and albumin were determined using standard methods. Results: Relative to baseline values, coffee consumption raised mean levels of ALT by 4 IU/l (p < 0.001), AST by 2.0 1 U/l (p < 0.001), ALP by 3.0 1 U/l (p < 0.01), total bilirubin by 0.90 mg/dl (p < 0.05) and total protein by 1.1 g/l (p < 0.05). Gender differences were observed. Significantly higher mean ALP concentration was only seen in male subjects, while mean bilirubin concentration was significantly raised in female volunteers alone. On the other hand, the mean total protein and albumin concentrations in individual male and female groups were not significantly altered (p > 0.05 in each case). Conclusion: The result obtained from the study suggests that short-term consumption of coffee might have a significant effect on the integrity of the liver function tests studied.
Ratio of hamstring to quadriceps femoris muscles' strength in the anterior cruciate ligament insufficient knee. Relationship to long-term recovery.

The purposes of this study were 1) to investigate the peak torque and total-work ratios of hamstring to quadriceps femoris muscles' (HQ) in 41 subjects (27 male, 14 female; means age = 35 years) with an anterior cruciate ligament insufficient knee (ACLIK) and 2) to determine the relationship between HQ ratios and long-term subject outcome. Quadriceps femoris and hamstring musculature strengths of both legs were measured at follow-up with an isokinetic dynamometer, and peak torque values were recorded at lower (60 degrees/sec) and higher (180 degrees/sec) speeds. Maximal isometric extension and flexion outputs were measured at a 60-degree knee-flexion angle. Three standardized knee-scoring scales were used to determine the overall outcome of the ACLIK. High intersubject variability of the HQ ratios (range = 23%-205%) was observed in all strength tests, including tests of healthy knees. The injured knee of all subjects had a higher HQ ratio (46%-95%) in every test than the healthy knee (42%-85%). The HQ ratio difference between knees was significant at the isokinetic higher speed (p less than .05) and for the total-work (p less than .05) tests because of the weak quadriceps femoris muscle of the injured knee. Outcome scores did not differ significantly between the groups with low, optimal, or high HQ ratios of the ACLIK but were significantly better in subjects whose HQ ratio of the injured knee was similar to that of their uninjured knee. (ABSTRACT TRUNCATED AT 250 WORDS)
Tissue Specificity of a Human Mitochondrial Disease

Background: ISCU myopathy is a disease caused by muscle-specific deficiency of the Fe-S cluster scaffold protein ISCU. Results: MyoD expression enhanced ISCU mRNA mis-splicing, and oxidative stress exacerbated ISCU depletion in patient cells. Conclusion: ISCU protein deficiency in patients results from muscle-specific mis-splicing as well as oxidative stress. Significance: Oxidative stress negatively influences the mammalian Fe-S cluster assembly machinery by destabilization of ISCU. Iron-sulfur (Fe-S) cluster cofactors are formed on the scaffold protein ISCU. ISCU myopathy is a disease caused by an intronic mutation that leads to abnormally spliced ISCU mRNA. We found that two predominant mis-spliced ISCU mRNAs produce a truncated and short-lived ISCU protein product in multiple patient cell types. Expression of the muscle-specific transcription factor MyoD further diminished normal splicing of ISCU mRNA in patient myoblasts, demonstrating that the process of muscle differentiation enhances the loss of normal ISCU mRNA splicing. ISCU protein was nearly undetectable in patient skeletal muscle, but was higher in patient myoblasts, fibroblasts, and lymphoblasts. We next treated patient cells with pro-oxidants to mimic the oxidative stress associated with muscle activity. Brief hydrogen peroxide treatment or incubation in an enriched oxygen atmosphere led to a marked further reduction of ISCU protein levels, which could be prevented by pretreatment with the antioxidant ascorbate. Thus, we conclude that skeletal muscle differentiation of patient cells causes a higher degree of abnormal ISCU splicing and that oxidative stress resulting from skeletal muscle work destabilizes the small amounts of normal ISCU protein generated in patient skeletal muscles.