Miracle-dz/UniFAR-FTUs huggingface dataset:
Two-subunit DNA escort mechanism and inactive subunit bypass in an ultra-fast ring ATPase

SpoIIIE is a homo-hexameric dsDNA translocase responsible for completing chromosome segregation in Bacillus subtilis. Here, we use a single-molecule approach to monitor SpoIIIE translocation when challenged with neutral-backbone DNA and non-hydrolyzable ATP analogs. We show that SpoIIIE makes multiple essential contacts with phosphates on the 5'→3' strand in the direction of translocation. Using DNA constructs with two neutral-backbone segments separated by a single charged base pair, we deduce that SpoIIIE’s step size is 2 bp. Finally, experiments with non-hydrolyzable ATP analogs suggest that SpoIIIE can operate with non-consecutive inactive subunits. We propose a two-subunit escort translocation mechanism that is strict enough to enable SpoIIIE to track one DNA strand, yet sufficiently compliant to permit the motor to bypass inactive subunits without arrest. We speculate that such a flexible mechanism arose for motors that, like SpoIIIE, constitute functional bottlenecks where the inactivation of even a single motor can be lethal for the cell. DOI: http://dx.doi. org/10.7554/eLife.09224. 001
Increased genomic alteration complexity and telomere shortening in B-CLL cells resistant to radiation-induced apoptosis

B-cell chronic lymphocytic leukemia (B-CLL) results in an accumulation of mature CD5+/CD23+ B cells due to an uncharacterized defect in apoptotic cell death. B-CLL is not characterized by a unique recurrent genomic alteration but rather by genomic instability giving rise frequently to several chromosomal aberrations. Besides we reported that ∼15% of B-CLL patients present malignant B-cells resistant to irradiation-induced apoptosis, contrary to ∼85% of patients and normal human lymphocytes. Telomere length shortening is observed in radioresistant B-CLL cells. Using fluorescence in situ hybridization (FISH) and multicolour FISH, we tested whether specific chromosomal aberrations might be associated with the radioresistance of a subset of B-CLL cells and whether they are correlated with telomere shortening. In a cohort of 30 B-CLL patients, all of the radioresistant B-CLL cell samples exhibited homozygous or heterozygous deletion of 13q14.3 in contrast to 52% of the radiosensitive samples. In addition to the 13q14.3 deletion, ten out of the 11 radioresistant B-cell samples had another clonal genomic alteration such as trisomy 12, deletion 17p13.1, mutation of the p53 gene or translocations in contrast to only three out of 19 radiosensitive samples. Telomere fusions and non-reciprocal translocations, hallmarks of telomere dysfunction, are not increased in radioresistant B-CLL cells. These findings suggest (i) that the 13q14.3 deletion accompanied by another chromosomal aberration is associated with radioresistance of B-CLL cells and (ii) that telomere shortening is not causative of increased clonal chromosomal aberrations in radioresistant B-CLL cells.
Duration to Establish an Emergency Vascular Access and How to Accelerate It: A Simulation-Based Study Performed in Real-Life Neonatal Resuscitation Rooms

Objectives: To compare the duration to establish an umbilical venous catheter and an intraosseous access in real hospital delivery rooms and as a secondary aim to assess delaying factors during establishment and to provide recommendations to accelerate vascular access in neonatal resuscitation. Design: Retrospective analysis of audio-video recorded neonatal simulation training. Settings: Simulation training events in exact replications of actual delivery/resuscitation rooms of 16 hospitals with different levels of care (Austria and Germany). Equipment was prepared the same way as for real clinical events. Subjects: Medical teams of four to five persons with birth-related background (midwives, nurses, neonatologists, and anesthesiologists) in a realistic team composition. Interventions: Audio-video recorded mannequin-based simulated resuscitation of an asphyxiated newborn including the establishment of either umbilical venous catheter or intraosseous access. Measurements and Main Results: The duration of access establishment (time from decision to first flush/aspiration), preparation (decision to start of procedure), and the procedure itself (start to first flush/aspiration) was significantly longer for umbilical venous catheter than for intraosseous access (overall duration 199 vs 86 s). Delaying factors for umbilical venous catheter establishment were mainly due to the complex approach itself, the multitude of equipment required, and uncertainties about necessary hygiene standards. Challenges in intraosseous access establishment were handling of the unfamiliar material and absence of an intraosseous access kit in the resuscitation room. There was no significant difference between the required duration for access establishment between large centers and small hospitals, but a trend was observed that duration for umbilical venous catheter was longer in small hospitals than in centers. Duration for intraosseous access was similar in both hospital types. Conclusions: Vascular access establishment in neonatal resuscitation could be accelerated by infrastructural improvements and specific training of medical teams. In simulated in situ neonatal resuscitation, intraosseous access is faster to establish than umbilical venous catheter. Future studies are required to assess efficacy and safety of both approaches in real resuscitation settings.
A redundancy of processes that cause replication fork stalling enhances recombination at two distinct sites in yeast rDNA

DNA recombination was investigated by monitoring integration at the rDNA of a circular minichromosome containing a 35S minigene and a replication fork barrier (RFB). The effects of replication fork stalling on integration were studied in wild‐type, FOB1Δ, SIR2Δ and the double mutant FOB1ΔSIR2Δ cells. The results obtained confirmed that Sir2p represses and replication fork stalling enhances integration of the minichromosome. This integration, however, only took place at two distinct sites: the RFB and the 3′ end of the 35S gene. For integration to take place at the 35S gene, replication fork stalling must occur at the 3′ end of the gene in both the minichromosome and the chromosomal repeats. Integration at the RFB, on the other hand, occurred readily in FOB1Δ cells, indicating that more than a single mechanism triggers homologous recombination at this site. Altogether, these observations strongly suggest that the main role for replication fork stalling at the rDNA locus is to promote homologous recombination rather than just to prevent head‐on collision of transcription and replication as originally thought.
TPF induction chemotherapy and concomitant irradiation with cisplatin and cetuximab in unresectable squamous cell carcinoma of the head and neck

The purpose of this study was to assess the efficacy and toxicity of docetaxel, cisplatin/5‐fluorouracil (TPF) induction chemotherapy and concomitant immunochemoradiotherapy with cetuximab and cisplatin in unresectable head and neck carcinoma.
A Flexible View on Prices

This paper argues that the flexible price paradigm is superior to the sticky price paradigm in the context of general equilibrium models. Based on a quarterly data set for six G7 economies, the paper presents two types of evidence showing that prices respond significantly to their underlying fundamentals. First, prices respond contemporaneously and significantly to technology shocks in all countries. Second, the cyclical correlation between prices and unit labor costs is highest contemporaneously and around 0.8 in all cases. This behavior is only consistent with a model where most firms set prices flexibly.
Inhibition of CaMKK2 Enhances Fracture Healing by Stimulating Indian Hedgehog Signaling and Accelerating Endochondral Ossification

Approximately 10% of all bone fractures do not heal, resulting in patient morbidity and healthcare costs. However, no pharmacological treatments are currently available to promote efficient bone healing. Inhibition of Ca2+/calmodulin (CaM)‐dependent protein kinase kinase 2 (CaMKK2) reverses age‐associated loss of trabecular and cortical bone volume and strength in mice. In the current study, we investigated the role of CaMKK2 in bone fracture healing and show that its pharmacological inhibition using STO‐609 accelerates early cellular and molecular events associated with endochondral ossification, resulting in a more rapid and efficient healing of the fracture. Within 7 days postfracture, treatment with STO‐609 resulted in enhanced Indian hedgehog signaling, paired‐related homeobox (PRX1)‐positive mesenchymal stem cell (MSC) recruitment, and chondrocyte differentiation and hypertrophy, along with elevated expression of osterix, vascular endothelial growth factor, and type 1 collagen at the fracture callus. Early deposition of primary bone by osteoblasts resulted in STO‐609–treated mice possessing significantly higher callus bone volume by 14 days following fracture. Subsequent rapid maturation of the bone matrix bestowed fractured bones in STO‐609–treated animals with significantly higher torsional strength and stiffness by 28 days postinjury, indicating accelerated healing of the fracture. Previous studies indicate that fixed and closed femoral fractures in the mice take 35 days to fully heal without treatment. Therefore, our data suggest that STO‐609 potentiates a 20% acceleration of the bone healing process. Moreover, inhibiting CaMKK2 also imparted higher mechanical strength and stiffness at the contralateral cortical bone within 4 weeks of treatment. Taken together, the data presented here underscore the therapeutic potential of targeting CaMKK2 to promote efficacious and rapid healing of bone fractures and as a mechanism to strengthen normal bones. © 2018 American Society for Bone and Mineral Research.
Biocompatibility of various root canal filling materials ex vivo.

AIM To evaluate the biocompatibility of a resin-based endodontic filler (RealSeal) using the indirect cytotoxicity test. METHODOLOGY Human gingival fibroblasts were cultured ex vivo. Pellets of the materials to be tested were incubated for 24, 48, and 72 h at 37 degrees C under sterile conditions to obtain their eluates. The fibroblasts were exposed to either diluted (50%) or undiluted eluates for 24 h. A culture medium with foetal calf serum was added to the control wells. Cell viability was estimated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method. The data concerning cell viability were statistically analyzed using one-way anova test and Bonferroni multiple comparisons test. RESULTS Eluates obtained after 24 h of incubation with the resin filler did not reduce cellular viability. An increase in cellular viability, as compared with control cells, was observed in the gutta-percha group. The undiluted eluate from the polyether material was cytotoxic, causing an 82 +/- 4% decrease in cellular viability. Eluates obtained after 48 h of incubation with the resin filler increased cellular viability, whereas the polyether significantly reduced viability. Gutta-percha did not cause any detectable change. After 72 h of incubation the eluate of the resin filler caused an increase in cellular viability, as did gutta-percha, whereas polyether caused a significant decrease. CONCLUSIONS RealSeal resin filler was nontoxic in this laboratory model. Further investigations are necessary to verify its usefulness in clinical applications.
An Evaluation of Poverty Prevalence in China: New Evidence from Four Recent Surveys

Knowledge of actual poverty prevalence is important for any society concerned with improving public welfare and reducing poverty. In this paper, we calculate and compare the poverty incidence rate in China using four nationally representative surveys: the China Family Panel Studies (CFPS) of 2010, the Chinese General Social Survey (CGSS) of 2010, the Chinese Household Finance Survey (CHFS) of 2011, and the Chinese Household Income Project (CHIP) of 2007.
Intake, feeding behaviour, digestibility, performance, carcass characteristics and meat quality of lambs fed different levels of semi-purified glycerine in the diet

ABSTRACT The aim of this study was to evaluate the effect of different inclusion levels of semi-purified glycerine in the diet of feedlot lambs on feeding behaviour, nutrient intake and digestibility, carcass characteristics, meat quality and in vitro degradability. Thirty-two Dorper × (Texel × Suffolk) crossbred intact male lambs (22.2 ± 5.51 kg) were fed glycerine (90% purity) at 0, 120, 240 or 360 g/kg dry matter (DM) in a total mixed ration with a roughage to concentrate ratio of 40:60 for 84 d. In vitro degradability was not affected by glycerine supplementation. Feeding behaviour and digestibility of DM, crude protein and fibre and production performance were similar among treatments. Ether extract digestibility was lower at the highest inclusion level. Glycerine level had no effect on ruminal pH, carcass characteristics and meat quality, except for subcutaneous fat thickness which was lower for lambs fed glycerine at 240 and 360 g/kg DM. Scores for unpleasant taste, unpleasant odour, succulence and softness of meat were not affected by dietary glycerine level. These data suggest that there are no adverse effects on carcass quality and performance when semi-purified glycerine is provided up to 360 g/kg DM in the diet of growing lambs fed a forage to concentrate ratio of 40:60.
Prediction strength modulates responses in human area CA 1 to 2 sequence violations 3 4 5

23 24 Emerging human, animal, and computational evidence suggests that, within the 25 hippocampus, stored memories are compared to current sensory input to compute 26 novelty – i.e., detecting when inputs deviate from expectations. Hippocampal subfield 27 CA1 is thought to detect mismatches between past and present, and detected novelty is 28 thought to modulate encoding processes, providing a mechanism for gating the entry of 29 information into memory. Using high-resolution functional MRI, we examined human 30 hippocampal subfield and medial temporal lobe (MTL) cortical activation during 31 prediction violations within a sequence of events unfolding over time. Subjects 32 encountered sequences of four visual stimuli that were then re-encountered in the 33 same temporal order (Repeat) or a rearranged order (Violation). Prediction strength was 34 manipulated by varying whether the sequence was initially presented once (Weak) or 35 thrice (Strong) prior to the critical Repeat or Violation sequence. Analyses of BOLD 36 signals revealed that task-responsive voxels in anatomically defined CA1, CA23/dentate 37 gyrus, and perirhinal cortex were more active when expectations were violated than 38 when confirmed. Additionally, stronger prediction violations elicited greater activity 39 than weaker violations in CA1, and CA1 contained the greatest proportion of voxels 40 displaying this prediction violation pattern relative to other MTL regions. Finally, a 41 memory test with a separate group of subjects showed that subsequent recognition 42 memory was superior for items that had appeared in prediction violation trials than in 43 prediction confirmation trials. These findings indicate that CA1 responds to temporal 44 order prediction violations and that this response is modulated by prediction strength. 45 46
The bystander effect in optically trapped red blood cells due to Plasmodium falciparum infection.

BACKGROUND In a previous study of the properties of red blood cells (RBC) trapped in an optical tweezers trap, an increase in the spectrum of Brownian fluctuations for RBCs from a Plasmodium falciparum culture (due to increased rigidity) compared with normal RBCs was measured. A bystander effect was observed, whereby RBCs actually hosting the parasite had an effect on the physical properties of remaining non-hosting RBCs. METHODS The distribution of corner frequency (fc) in the power spectrum of single RBCs held in an optical tweezers trap was studied. Two tests were done to confirm the bystander effect. In the first, RBCs from an infected culture were separated into hosting and non-hosting RBCs. In the second, all RBCs were removed from the infected culture, and normal RBCs were incubated in the spent medium. The trapping environment was the same for all measurements so only changes in the properties of RBCs were measured. RESULTS In the first experiment, a similar and statistically significant increase was measured both for hosting and non-hosting RBCs. In the second experiment, normal RBCs incubated in spent medium started to become rigid after a few hours and showed complete changes (comparable with RBCs from the infected culture) after 24 h. CONCLUSION These experiments provide direct evidence of medium-induced changes in the properties of RBCs in an infected culture, regardless of whether the RBCs actually host the parasite.
Why is Corruption a Problem of the State?

Economic theories of the last decades provide analytical framework within which we can explain institutional conditions for corrupt action. Specialists making economic policy recommendations to resolve this problem use several approaches, the most dominant of which are rent-seeking and agency theories. In this paper, I explain economic policy recommendations that stem out of both approaches. I argue that scholars suggesting these recommendations within these two frameworks do not understand each other because of different assumptions they make. More specifically, I show that two sets of policy recommendations presented here are based on the particular system of property rights assumed within each theory. In this example, I show why corruption is a problem of the state rather than the market.
The role of animal‐based attractions in ecological sustainability

Purpose – The purpose of this paper is to discuss the contribution of animal‐based attractions to ecological causes – particularly wildlife conservation and environmental education – while portraying the debate regarding the legitimacy and effectiveness of these sites.Design/methodology/approach – An extensive literature review gives examples, demonstrating the potential of animal‐based attractions to support the causes of ecological sustainability while raising the challenges, constraints, and limitations in utilizing them to the fullest.Findings – Opposition to animal‐based attractions is fierce and should be understood and addressed by management and regional associations.Practical implications – Suggestions for improving the sites' operations are elaborated throughout the paper.Originality/value – The paper is of value to relevant stakeholders including zoological professionals and animal activists, and it can raise awareness of certain aspects that may not have received adequate attention.
A maternal high‐fat diet modulates fetal SIRT1 histone and protein deacetylase activity in nonhuman primates

In nonhuman primates, we previously demonstrated that a maternal high‐fat diet (MHFD) induces fetal nonalcoholic fatty liver disease (NAFLD) and alters the fetal metabolome. These changes are accompanied by altered acetylation of histone H3 (H3K14ac). However, the mechanism behind this alteration in acetylation remains unknown. As SIRT1 is both a lysine deacetylase and a crucial sensor of cellular metabolism, we hypothesized that SIRT1 may be involved in fetal epigenomic alterations. Here we show that in utero exposure to a MHFD, but not maternal obesity per se, increases fetal H3K14ac with concomitant decreased SIRT1 expression and diminished in vitro protein and histone deacetylase activity. MHFD increased H3K14ac and DBC1‐SIRT1 complex formation in fetal livers, both of which were abrogated with diet reversal despite persistent maternal obesity. Moreover, MHFD was associated with altered expression of known downstream effectors deregulated in NAFLD and modulated by SIRT1 (e.g., PPARA, PPARG, SREBF1, CYP7A1, FASN, and SCD). Finally, ex vivo purified SIRT1 retains deacetylase activity on an H3K14ac peptide substrate with preferential activity toward acetylated histone H3; mutagenesis of the catalytic domain of SIRT1 (H363Y) abrogates H3K14ac deacetylation. Our data implicate SIRT1 as a likely molecular mediator of the fetal epigenome and metabolome under MHFD conditions. —Suter, M. A. , Chen, A. , Burdine, M. S. , Choudhury, M. , Harris, R. A. , Lane, R. H. , Friedman, J. E. , Grove, K. L. , Tackett, A. J., Aagaard, K. M. A maternal high‐fat diet modulates fetal SIRT1 histone and protein deacetylase activity in nonhuman primates. FASEB J. 26, 5106–5114 (2012). www.fasebj. org
Glial localization of antiquitin: Implications for pyridoxine‐dependent epilepsy

A high incidence of structural brain abnormalities has been reported in individuals with pyridoxine‐dependent epilepsy (PDE). PDE is caused by mutations in ALDH7A1, also known as antiquitin. How antiquitin dysfunction leads to cerebral dysgenesis is unknown. In this study, we analyzed tissue from a child with PDE as well as control human and murine brain to determine the normal distribution of antiquitin, its distribution in PDE, and associated brain malformations.
A Cluster Analysis of Personality Style in Adults With ADHD

Objective: The purpose of this study was to use hierarchical linear cluster analysis to examine the normative personality styles of adults with ADHD. Method: A total of 311 adults with ADHD completed the Millon Index of Personality Styles, which consists of 24 scales assessing motivating aims, cognitive modes, and interpersonal behaviors. Results: The sample was randomly divided into half, and independent hierarchical linear cluster analyses were performed on each half to identify replicable clusters. A three-cluster solution was selected, and two of the clusters were replicated across the independent analyses. Participants in Cluster 1 manifested more polarized, negative motivating aims, cognitive modes, and interpersonal behaviors than participants in Cluster two. Conclusion: Hierarchical linear cluster analyses identified two very different personality styles in a sample of adults with ADHD, with implications for clinicians and future research. (J. of Att. Dis. 2008; 12(3) 254-263)
Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in rhesus macaque brain

Long noncoding RNAs (lncRNAs) mediate important epigenetic regulation in a wide range of biological processes and diseases. We applied comprehensive analyses of RNA-seq and CAGE-seq (cap analysis of gene expression and sequencing) to characterize the dynamic changes in lncRNA expression in rhesus macaque (Macaca mulatta) brain in four representative age groups. We identified 18 anatomically diverse lncRNA modules and 14 mRNA modules representing spatial, age, and sex specificities. Spatiotemporal- and sex-biased changes in lncRNA expression were generally higher than those observed in mRNA expression. A negative correlation between lncRNA and mRNA expression in cerebral cortex was observed and functionally validated. Our findings offer a fresh insight into spatial-, age-, and sex-biased changes in lncRNA expression in macaque brain and suggest that the changes represent a previously unappreciated regulatory system that potentially contributes to brain development and aging.