Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of the Herpes Simplex Virus Type-1 UL9 DNA Helicase by Its Cognate Single-strand DNA-binding Protein, ICP8*

The mechanism of stimulation of a DNA helicase by its cognate single-strand DNA-binding protein was examined using herpes simplex virus type-1 UL9 DNA helicase and ICP8. UL9 and ICP8 are two essential components of the viral replisome that associate into a complex to unwind the origins of replication. The helicase and DNA-stimulated ATPase activities of UL9 are greatly elevated as a consequence of this association. Given that ICP8 acts as a single-strand DNA-binding protein, the simplest model that can account for its stimulatory effect predicts that it tethers UL9 to the DNA template, thereby increasing its processivity. In contrast to the prediction, data presented here show that the stimulatory activity of ICP8 does not depend on its single-strand DNA binding activity. Our data support an alternative hypothesis in which ICP8 modulates the activity of UL9. Accordingly, the data show that the ICP8-binding site of UL9 constitutes an inhibitory region that maintains the helicase in an inefficient ground state. ICP8 acts as a positive regulator by neutralizing this region. ICP8 does not affect substrate binding, ATP hydrolysis, or the efficiency of translocation/DNA unwinding. Rather, we propose that ICP8 increases the efficiency with which substrate binding and ATP hydrolysis are coupled to translocation/DNA unwinding.
Involvement of site‐specific FAK phosphorylation in sphingosine‐1 phosphate‐ and thrombin‐induced focal adhesion remodeling: role of Src and GIT

Sphingosine‐1 phosphate (S1P) and thrombin are agents with profound but divergent ef‐ fects on vascular endothelial cell (EC) barrier proper‐ ties. We have previously reported that S1P‐induced focal adhesion (FA) remodeling involves interactions between focal adhesion kinase (FAK), paxillin, and G‐protein‐coupled receptor kinase‐interacting proteins GIT1 and GIT2 and suggested a critical involvement of focal adhesions in the EC barrier regulation. In this study, we examined redistribution of FA proteins (FAK, paxillin, GIT1, and GIT2) and site‐specific FAK ty‐ rosine phosphorylation in human pulmonary artery endothelial cells stimulated with thrombin. In contrast to S1P, which we have shown to induce peripheral translocation of FA proteins associated with cortical actin ring formation, thrombin caused the redistribution of FA proteins to the ends of the newly formed massive stress fibers. S1P and thrombin induced dis‐ tinct patterns of FAK site‐specific phosphorylation with the FAK Y576 phosphorylation site targeted by SIP challenge and phosphorylation of three FAK sites (Y397, Y576, and Y925) in response to thrombin stimulation. Pharmacological inhibition of Src with Src‐specific in‐ hibitor PP2 abolished S1P‐induced translocation of FA proteins, cortical actin ring formation, and FAK [Y576] phosphorylation. However, PP2 failed to alter throm‐ bin‐induced morphological changes and exhibited only partial inhibition of FAK site‐specific tyrosine phos‐ phorylation. These observations highlight the differen‐ tial mechanisms of focal adhesion protein complex remodeling and FAK activation by S1P and thrombin and link differential FA remodeling to EC barrier regulation. —Shikata, Y. , Birukov, K. G. , Birukova, A. A. , Verin, A. , Garcia, J. G. N. Involvement of site‐specific FAK phosphorylation in sphingosine‐1 phosphate‐ and thrombin‐induced focal adhesion re‐ modeling: role of Src and GIT. FASEB J. 17, 2240‐2249 (2003)
Is adiposity an under-recognized risk factor for tendinopathy? A systematic review.

OBJECTIVE Tendon injuries have been reported to occur more frequently in individuals with increased adiposity. Treatment also appears to have poorer outcomes among these individuals. Our objective was to examine the extent and consistency of associations between adiposity and tendinopathy. METHODS A systematic review of observational studies was conducted. Eight electronic databases were searched (Allied and Complementary Medicine, Biological Abstracts, CINAHL, Current Contents, EMBase, Medline, SPORTDiscus, and Web of Science) and citation tracking was performed on included reports. Studies were included if they compared adiposity between subjects with and without tendon injury or examined adiposity as a predictor of conservative treatment success. RESULTS Four longitudinal cohorts, 14 cross-sectional studies, 8 case-control studies, and 2 interventional studies (28 in total) met the inclusion criteria, providing a total of 19,949 individuals. Forty-two subpopulations were identified, 18 of which showed elevated adiposity to be associated with tendon injury (43%). Sensitivity analyses indicated a clustering of positive findings among studies that included clinical patients (81% positive) and among case-control studies (77% positive). CONCLUSION Elevated adiposity is frequently associated with tendon injury. Published reports suggest that elevated adiposity is a risk factor for tendon injury, although this association appears to vary depending on aspects of study design and measurement. Adiposity is of particular interest in tendon research because, unlike a number of other reported risk factors for tendon injury, it is somewhat preventable and modifiable. Further research is required to determine if reducing adiposity will reduce the risk of tendon injury or improve the results of treatment.
Wealth and Income Distribution: New theories Needed for a New Era

Growth theories traditionally focus on the Kaldor­Kuznets stylised facts. Ravi Kanbur and Nobelist Joe Stiglitz argue that these no longer hold; new theory is needed. The new models need to drop competitive marginal productivity theories of factor returns in favour of rent­generating mechanism and wealth inequality by focusing on the 'rules of the game. ' They also must model interactions among physical, financial, and human capital that influence the level and evolution of inequality. A third key component will be to capture mechanisms that transmit inequality from generation to generation. Six decades ago, Nicholas Kaldor (1957) put forward a set of stylised facts on growth and distribution for mature industrial economies. The first and most prominent of these was the constancy of the share of capital relative to that of wealth in national income. At about the same time, Simon Kuznets (1955) put forward a second set of stylised facts ­­ that while the interpersonal inequality of income distribution might increase in the early stages of development, it declines as industrialised economies mature. These empirical formulations brought forth a generation of growth and development theories whose object was to explain the stylised facts. Kaldor himself presented a growth model which claimed to produce outcomes consistent with constancy of factor shares, as did Robert Solow. Kuznets also developed a model of rural­urban transition consistent with his prediction, as did many others (Kanbur 2012). Kaldor­Kuznets facts no longer hold However, the Kaldor­Kuznets stylised facts no longer hold for advanced economies. The share of capital as conventionally measured has been on the rise, as has interpersonal inequality of income and wealth. Of course, there are variations and subtleties of data and interpretation, and the pattern is not uniform. But these are the stylised facts of our time. Bringing these facts centre stage has been the achievement of research leading up to Piketty (2014). It stands to reason that theories developed to explain constancy of factor shares cannot explain a rising share of capital. The theories developed to explain the earlier stylised facts cannot very easily explain the new trends, or the turnaround. At the same time, rising inequality has opened once again a set of questions on the normative significance of inequality of outcomes versus inequality of opportunity. New theoretical developments are needed for positive and normative analysis in this new era. What sort of new theories? In the realm of positive analysis, Piketty …
Women with inflammatory polyarthritis have babies of lower birth weight.

OBJECTIVE To assess the effect on fetal outcome, and development of the child over the first 8 months of life, of rheumatoid arthritis (RA) during pregnancy. METHODS Women with RA or undifferentiated inflammatory polyarthritis (IP) were recruited from throughout the UK and followed prospectively from late pregnancy to 8 months postpartum. Matched controls were obtained from general practitioners. The babies' health at birth and development at 8 months were monitored by the weight, head circumference, and length. Potential confounding variables were noted. RESULTS One hundred thirty-three women with RA or undifferentiated IP took part in the study. There were 5 (4%) admissions for hypertension during pregnancy and no cases of preeclampsia. Cesarean section was common (23%). Matched controls were found for 103 (77%) subjects. There were no significant differences between groups in head circumference or length at birth. Babies born to women with arthritis had lower mean birth weight than controls [3.3 kg (standard deviation 0.5) compared to 3.5 kg (0.4); p = 0.004], even after adjustment for potential confounding factors. Within the patient group those whose arthritis was in remission had significantly heavier babies than those with active disease [mean 3.5 kg (0.5) compared with 3.3 kg (0.5); p = 0.04]. This trend was still apparent at 8 months, but differences were no longer statistically significant. CONCLUSION This is the first relatively large prospective study of the effects on mother and baby of RA during pregnancy. The results suggest that, although disease improves in most women during pregnancy, it is still sufficiently active to have a modest negative effect on birth weight.
Full‐Scale Class A Biosolids Production by Two‐Stage Continuous‐Batch Thermophilic Anaerobic Digestion at the Hyperion Treatment Plant, Los Angeles, California

The City of Los Angeles Hyperion Treatment Plant (HTP) (California) converted its anaerobic digesters to thermophilic operation to produce Class A biosolids. Phase IV tests demonstrated compliance of a two‐stage, continuous‐batch process with Alternative 1 of U.S. Environmental Protection Agency 40 CFR Part 503 (U.S. EPA, 1993), which defines the time–temperature requirement for batch treatment (T ≥ 56.3°C at 16‐h holding). Fecal coliforms, Salmonella sp. , viable helminth ova, and enteric viruses were not detected in biosolids in the postdigestion train, including the truck‐loading facility and the farm for land application as the last points of plant control where compliance is to be demonstrated. The same results were achieved during Phase V tests, after lowering the second‐stage holding temperature to 52.6°C to reduce the elevated methyl mercaptan production that was observed during Phase IV. Hence, the Phase V process complied with Alternative 3 of 40 CFR Part 503. Currently, HTP operates its digesters under the same conditions as tested in Phase V. In 2003, monthly monitoring of the biosolids at the truck‐loading facility and the farm for land application demonstrated consistent compliance with Alternative 3.
Coping with coopetition
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 Facing dilemmas in cooperation for sustainable development: The case of the Dutch smart grid industry

This paper is amongst the first to examine coopetition strategy for sustainable development at the network level. Companies who want to successfully implement complex innovative technologies that support sustainable development need to collaborate with other actors of the innovation ecosystem, including their competitors, so that they can develop standards, interoperable products, pool knowledge, and resources and bundle forces to compete against other technologies. Collaboration with competitors brings benefits, but also many risks. We investigated how firms cope with these risks when establishing an innovation ecosystem to implement a new technology in society. We conducted research in the Dutch smart grids sector and explored how these firms minimize inherent risks of coopetition. We found that system-building actors in the Dutch smart grid field not only minimize inherent risks, but from the start of their collaboration they implement so-called enablers to prevent these risks upfront.
Genetic structure of Siberian lemmings (Lemmus sibiricus) in a continuous habitat: large patches rather than isolation by distance

In a continuous habitat, restricted dispersal and local genetic drift are likely to create a pattern of increasing genetic differentiation with distance. Here, we describe the genetic structure of Siberian lemming (Lemmus sibiricus) populations in a continuous tundra habitat on the western coast of the Taimyr Peninsula, in order to determine the spatial scale at which genetic differentiation and isolation by distance occur. Sampling was carried out at three different geographical scales: (1) a continuous 11 km transect; (2) localities 10–30 km apart; and (3) two localities at 300 and 600 km from the main study area. Two types of genetic markers were used: partial sequences of the mitochondrial DNA control region and four microsatellite loci. On this basis the study populations were genetically quite homogeneous within patches extending over 8 km or more. Contrary to theoretical predictions, no pattern of isolation by distance among patches could be identified. This observation was interpreted as representing populations in migration–drift disequilibrium after a recent major mixing event. The lack of concordance between mtDNA haplotype phylogeny and the geographical distribution of haplotypes supported this interpretation. Spatial autocorrelation among individual genotypes on a local scale was weak and observed only in females, indicating a considerable amount of mostly male-mediated gene flow. Average gene flow per generation was estimated to be in the range of several hundred metres.
Double-blind, placebo-controlled trial of the pain-relieving effects of the implantation of gold beads into dogs with hip dysplasia

Seventy-eight dogs with pain due to hip dysplasia were studied in a controlled, double-blind clinical trial to evaluate gold bead implantation as a pain-relieving treatment. The dogs were randomly assigned to two groups, 36 in the gold implantation group and 42 in the placebo group. Both groups were treated equally regarding anaesthesia, hair clipping and penetration of the skin with the same type of needle. The gold implantation group had small pieces of 24 carat gold inserted through needles at five different acupuncture points and the placebo group had the skin penetrated at five non-acupuncture points so as to avoid any possible effect of stimulating the acupuncture points. A certified veterinary acupuncturist marked the points, and two surgeons performed the implantations according to a randomisation code made in advance. After 14 days, three months and six months, the owners assessed the overall effect of the treatments by answering a questionnaire, and the same veterinarian examined each dog and evaluated its degree of lameness by examining videotaped footage of it walking and trotting. The treatment was blinded for both the owners and the veterinarian. There were significantly greater improvements in mobility and greater reductions in the signs of pain in the dogs treated with gold implantation than in the placebo group. The veterinarian’s and the owners’ assessments corresponded well.
UDP-sugar Pyrophosphorylase with Broad Substrate Specificity Toward Various Monosaccharide 1-Phosphates from Pea Sprouts*

UDP-sugars, activated forms of monosaccharides, are synthesized through de novo and salvage pathways and serve as substrates for the synthesis of polysaccharides, glycolipids, and glycoproteins in higher plants. A UDP-sugar pyrophosphorylase, designated PsUSP, was purified about 1,200-fold from pea (Pisum sativum L.) sprouts by conventional chromatography. The apparent molecular mass of the purified PsUSP was 67,000 Da. The enzyme catalyzed the formation of UDP-Glc, UDP-Gal, UDP-glucuronic acid, UDP-l-arabinose, and UDP-xylose from respective monosaccharide 1-phosphates in the presence of UTP as a co-substrate, indicating that the enzyme has broad substrate specificity toward monosaccharide 1-phosphates. Maximum activity of the enzyme occurred at pH 6.5–7.5, and at 45 °C in the presence of 2 mm Mg2+. The apparent Km values for Glc 1-phosphate and l-arabinose 1-phosphate were 0.34 and 0.96 mm, respectively. PsUSP cDNA was cloned by reverse transcriptase-PCR. PsUSP appears to encode a protein with a molecular mass of 66,040 Da (600 amino acids) and possesses a uridine-binding site, which has also been found in a human UDP-N-acetylhexosamine pyrophosphorylase. Phylogenetic analysis revealed that PsUSP can be categorized in a group together with homologues from Arabidopsis and rice, which is distinct from the UDP-Glc and UDP-N-acetylhexosamine pyrophosphorylase groups. Recombinant PsUSP expressed in Escherichia coli catalyzed the formation of UDP-sugars from monosaccharide 1-phosphates and UTP with efficiency similar to that of the native enzyme. These results indicate that the enzyme is a novel type of UDP-sugar pyrophosphorylase, which catalyzes the formation of various UDP-sugars at the end of salvage pathways in higher plants.
Safety and Efficacy of Epinephrine Added to Bupivacaine for Lumbar Epidural Analgesia in Obstetrics

The effects of epidural bupivacaine with and without 1:300,000 epinephrine on uterine activity, progress of labor, fetal heart rate, maternal blood pressure and heart rate, newborn Apgar scores, neonatal acid—base status, and Neurologic and Adaptive Capacity Scoring System (NACS) were compared in 32 parturients during labor and delivery. Patients in group I (n = 16) received 0.5% bupivacaine with 1:300,000 epinephrine and those in group II (n = 16) received 0.5% bupivacaine alone. Addition of epinephrine to bupivacaine had no significant effects on uterine activity, duration of first or second stages of labor, fetal heart rate and variability, or the incidence of abnormal fetal heart rate patterns. Maternal hypotension occurred less frequently in group I than in group II patients (P < 0.05). Apgar scores, neonatal acid-base status, and the NACS were equally good in the two groups. Duration of analgesia was significantly longer in group I than in group II (186.8 ± 11.6 vs 85.3 ± 6.1 (mean ± sem) min, P < 0.001). It is concluded that adding epinephrine to bupivacaine during epidural anesthesia in the normal parturient has no adverse effects on either mother, fetus, neonate, or the progress of labor; and that it significantly prolongs the duration of anesthesia and decreases the incidence of maternal hypotension.
Heteroduplex Analysis of the Sequence Relationships Between the Genomes of Kirsten and Harvey Sarcoma Viruses, Their Respective Parental Murine Leukemia Viruses, and the Rat Endogenous 30S RNA

The sequence relations between Kirsten murine sarcoma virus (Ki-SV), Harvey murine sarcoma virus (Ha-SV), and a rat endogenous 30S RNA were studied by electron microscope heteroduplex analysis. The sequence relationships between the sarcoma viruses and their respective parental murine leukemia viruses (Kirsten and Moloney murine leukemia viruses), as well as between the two murine leukemia viruses, were also studied. The only observed nonhomology feature of the Kirsten murine leukemia virus/Moloney murine leukemia virus heteroduplexes was a substitution loop with two arms of equal length extending from 1.80 ± 0.18 kilobases (kb) to 2.65 ± 0.27 kb from the 3′ end of the RNA. It is believed that this feature lies in the env gene region of the viral genomes. The Ha-SV and Moloney murine leukemia virus genomes (respective lengths, 6.0 and 9.0 kb) were homologous in a 1.0 ± 0.05-kb region at the 3′ end and possibly over a 200-nucleotide region at the 5′ ends; otherwise, they were nonhomologous. Ha-SV and Ki-SV (length, 7.5 kb) were homologous in the first 4.36 ± 0.37-kb region from the 3′ end and in a 0.70 ± 0.15-kb region at the 5′ end. In between, there was a nonhomology region, possibly containing a short (0.23-kb) region of partial or total homology. The heteroduplex analysis between rat endogenous 30S RNA and Ki-SV shows that there are mixed regions of sequence homology and nonhomology at both the 5′ and 3′ ends. However, there is a large (4-kb) region of homology between Ki-SV and the rat 30S RNA in the center of the genomes, with only a small nonhomology hairpin feature. These studies help to define the regions of homology between the Ha-SV and Ki-SV genomes with each other and with the rat endogenous 30S RNA. These regions may be related to the sarcoma genicity of the viruses. In particular, the 0.7-kb region of homology of Ha-SV with Ki-SV at the 5′ ends may be related to the formation of a 21,000-dalton phosphoprotein in cells transformed by either virus.
White matter volume in alcohol use disorders: a meta‐analysis

Atrophy of brain white matter (WM) often is considered a signature injury of alcohol use disorders (AUDs). However, investigations into AUD‐related changes in WM volume have yielded complex findings that are difficult to synthesize in a narrative review. The objective of this study was to obtain an averaged effect size (ES) for WM volume reduction associated with AUD diagnosis and to test potential moderators of ES. Study inclusion criteria were: (1) English language; (2) peer reviewed; (3) published before December 2011; (4) use of magnetic resonance imaging (MRI); (5) human participants; (6) inclusion of AUD group; (7) inclusion of non‐AUD comparison group; and (8) reporting or testing of total or cerebral WM volume. Moderators included study design, MRI methodology and AUD characteristics. Nineteen studies with a total of 1302 participants (70% male) were included, and calculated ESs were confirmed by the corresponding author for 12 studies. The magnitude of the averaged ES adjusted for small sample bias (Hedges' g) for WM reduction in AUDs was 0.304 (standard error = 0.134, range = −0.57–1.21). Hierarchical linear modeling indicated that the overall ES differed significantly from 0, t(18) = 2.257, P = 0.037, and that the distribution of the 19 ESs showed significant heterogeneity beyond sampling error, χ2(18) = 52.400, P < 0.001. Treatment‐seeking status and length of abstinence were significant moderators of ES distribution. These results are suggestive of WM recovery with sustained abstinence and point to the need for further investigation of factors related to treatment‐seeking status.
The Role of Medical Expenditure Risk in Portfolio Allocation Decisions

Economic theory suggests that medical spending risk affects the extent to which households are willing to accept financial risk, and consequently their investment portfolios. In this study, we focus on the elderly for whom medical spending represents a substantial risk. We exploit the exogenous reduction in prescription drug spending risk because of the introduction of Medicare Part D in the U.S. in 2006 to identify the causal effect of medical spending risk on portfolio choice. Consistent with theory, we find that Medicare-eligible persons increased risky investment after the introduction of prescription drug coverage, relative to a younger, ineligible cohort. Copyright © 2016 John Wiley & Sons, Ltd.