Miracle-dz/UniFAR-FTUs huggingface dataset:
Escherichia coli single-stranded DNA-binding protein mediates template recycling during transcription by bacteriophage N4 virion RNA polymerase

Coliphage N4 virion RNA polymerase (vRNAP), the most distantly related member of the T7-like family of RNA polymerases, is responsible for transcription of the early genes of the linear double-stranded DNA phage genome. Escherichia coli single-stranded DNA-binding protein (EcoSSB) is required for N4 early transcription in vivo, as well as for in vitro transcription on super-coiled DNA templates containing vRNAP promoters. In contrast to other DNA-dependent RNA polymerases, vRNAP initiates transcription on single-stranded, promoter-containing templates with in vivo specificity; however, the RNA product is not displaced, thus limiting template usage to one round. We show that EcoSSB activates vRNAP transcription at limiting single-stranded template concentrations through template recycling. EcoSSB binds to the template and to the nascent transcript and prevents the formation of a transcriptionally inert RNA:DNA hybrid. Using C-terminally truncated EcoSSB mutant proteins, human mitochondrial SSB (Hsmt SSB), phage P1 SSB, and F episome-encoded SSB, as well as a Hsmt-EcoSSB chimera, we have mapped a determinant of template recycling to the C-terminal amino acids of EcoSSB. T7 RNAP contains an amino-terminal domain responsible for binding the RNA product as it exits from the enzyme. No sequence similarity to this domain exists in vRNAP. Hereby, we propose a unique role for EcoSSB: It functionally substitutes in N4 vRNAP for the N-terminal domain of T7 RNAP responsible for RNA binding.
The Natural History of Sciatica Associated with Disc Pathology: A Prospective Study with Clinical and Independent Radiologic Follow-Up

The purpose of this study was to assess the natural history of sciatica due to lumbosacral nerve root compromise and to evaluate the pathomorphologic changes that accompany the natural resolution of the disease. One hundred sixty-five consecutive patients, 114 males and 51 females, with an average age of 41 years (range, 17-72) and an average duration of symptoms of 4.2 months (range, 1-72) presenting with sciatica thought to be due to lumbosacral nerve root compromise were admitted to the study. The cornerstone of treatment was the serial epidural administration of steroid and local anesthetic by the caudal route on an outpatient basis. Lumbar epidural injection or periradicular infiltration at the appropriate level, confirmed under image intensifier, was the next step before considering surgical decompression. An average of three injections (range, 0-8) was received by each patient. Patients underwent clinical examination and computed tomography. Twenty-three patients (14%) underwent surgical decompression. The remainder were clinically assessed at 1 year after presentation, and 111 were rescanned at the appropriate levels. All conservatively managed patients made a satisfactory clinical recovery: average reduction of pain on the visual analog scale was 94% (range, 45-100), and 64 (76%) of the 84 disc herniations and 7 (26%) of the 27 disc bulges showed partial or complete resolution (chi-square = 20.27 P = 0.0001). Thus a high proportion of patients with discogenic sciatica make a satisfactory recovery with aggressive conservative management, and this recovery is accompanied by resolution of disc herniations in a significant number. Only a small proportion of patients needed surgical decompression.
Molecular Characterization of the PEND Protein, a Novel bZIP Protein Present in the Envelope Membrane That Is the Site of Nucleoid Replication in Developing Plastids

Plastid nucleoids are known to bind to the envelope membrane in developing chloroplasts. Here, plastid DNA is extensively replicated. We previously detected a DNA binding protein in the inner envelope membranes of developing plastids in pea and named it PEND (for plastid envelope DNA binding) protein. In this study, we report on the structure and molecular characterization of a cDNA for the PEND protein. As a result of screening cDNA libraries in λgt11 with one of the target sequences of the PEND protein as a probe, we obtained a clone (PD2) for a novel DNA binding protein consisting of 633 amino acid residues. Analysis of the N-terminal sequence of the purified PEND protein indicated that the transit peptide is just 16 residues long. The PEND protein was detected specifically in the plastid envelope membrane of young unopened leaf buds by immunoblot analysis. The PEND protein consists of a basic region plus zipper region, an unprecedented sextuple repeat region, and a putative membrane-spanning region. The basic region with a zipper region seems to have diverged from that of other plant transcription factors. In addition, the PEND protein could be a distant homolog of the trans-Golgi network integral membrane proteins. The PEND protein is therefore a novel type of DNA binding protein that binds to the membrane as an intrinsic membrane protein.
The absence of antagonism between extracts of Clinacanthus nutans Burm. and Naja naja siamensis venom.

Clinacanthus nutans Burm, a herb reputed in Thailand and Malaysia to be "snakebite antidote" has been tested in vitro and in vivo for antivenin activity. The aqueous extract of C. nutans leaves has been found to have no effect on the inhibition of neuromuscular transmission produced by purified Naja naja siamensis neurotoxin in isolated rat phrenic-nerve diaphragm preparations. The extract of C. nutans, when given orally or intraperitoneally, are ineffective in prolonging the survival time of experimental mice receiving lethal doses of N.n. siamensis crude venom. Oral administrations of the herb extracts pretreated with alpha-amylase or beta-amylase also fail to protect the animal. It is concluded that the extract of C. nutans can not antagonize the action of cobra venom.
Cutaneous CD30+ Cells in Children with Atopic Dermatitis

Background: CD30 expression can be considered a marker of Th2 cells. We investigated the presence of CD30+ cells in the lesional skin of children with atopic dermatitis (AD). We also analyzed the possible relationship between CD30+ cells and serum soluble CD 30 (sCD30) levels, and IgE, soluble interleukin-2 (IL-2) receptor (sIL-2R) or soluble CD23 (sCD23) levels in the blood, and clinical score. Methods: Ten eczematous children (4 males, 6 females; median age: 4 years and 5 months; range: 11 months to 14 years), 9 sex- and age-matched control children and an adult control group were studied. A clinical score (SCORAD index), was given to eczematous lesions. Blood was taken for the determination of IgE, sCD30, sIL-2R and sCD23 levels. Punch biopsies of lesional skin were stained with hematoxylin and eosin or incubated with anti-CD30 monoclonal antibodies. Skin prick tests (SPTs) were also performed. Results: In the biopsy specimens, CD30 expression was observed in high proportions of infiltrating cells. In children with AD, total serum IgE, sCD30, sIL-2R, sCD23 and eosinophils were significantly elevated compared to controls. CD30+ cells were not associated with serum IgE, sCD30, sIL-2R, sCD23, or SPT results, score of inflammatory cells in lesional skin or clinical score. Children with AD who had high total IgE and specific IgE antibodies did not differ from those with normal total IgE and negative specific IgE in respect of age, clinical score, number of CD30+ cells, sCD30, sIL-2R and sCD23 levels, score of inflammatory cells in skin or clinical score. Conclusion: Our results showed remarkable numbers of CD30+ cells in the lesional skin and high sCD30 in the serum of children with AD. CD30+ cells did not correlate with systemic markers of IgE reaction.
Complex paroxysmal nocturnal behaviors in Parkinson's disease

Complex paroxysmal nocturnal motor behavioral disorders (CPNBs) are frequently reported in patients with Parkinson's disease (PD). REM sleep behavior disorder (RBD) is reported in at least a third of PD patients, although CPNB episodes can also occur on arousal from NREM sleep. It is important to establish the nature of CPNBs occurring in PD, as the different types have different neurobiological significance and clinical importance, and also different treatments. Ninety‐six PD patients with and without CPNBs were submitted to overnight in‐hospital video‐polysomnography. Of these, 76 (47 men) were included in the study analysis: these were patients in whom it was possible to establish the presence or absence of CPNBs and to obtain a clear‐cut diagnosis of the nature of the CPNBs reported. The CPNBs were found to be RBD episodes in 39 cases (87%) and nonRBD episodes in 6 (13%) (arousal‐related episodes arising from NREM sleep in 3 cases and from REM sleep in 2 cases, parasomnia overlapping syndrome in 1 case). In 4 of the 6 subjects with nonRBD episodes, these occurred upon arousal at the end of an obstructive apnoeic event. Our data confirm that CPNBs in PD are, in most cases, RBD episodes. However, arousal‐related episodes accounted for 13% of the CPNBs observed in our sample and occurred in close temporal association with sleep‐disordered breathing (SDB). The arousal system is defective in extrapyramidal diseases due to neurodegenerative changes involving the brain stem reticular network; against this background, a trigger effect of SDB on CPNBs, through induction of abrupt arousal, may be hypothesized. © 2010 Movement Disorder Society
Characterization of and lipopolysaccharide binding to the E. coli LptC protein dimer

Lipopolysaccharide (LPS, endotoxin) is the major component of the outer leaflet of the outer membrane of Gram‐negative bacteria such as Escherichia coli and Salmonella typhimurium. LPS is a large lipid containing several acyl chains as its hydrophobic base and numerous sugars as its hydrophilic core and O‐antigen domains, and is an essential element of the organisms' natural defenses in adverse environmental conditions. LptC is one of seven members of the lipopolysaccharide transport (Lpt) protein family that functions to transport LPS from the inner membrane (IM) to the outer leaflet of the outer membrane of the bacterium. LptC is anchored to the IM and associated with the IM LptFGB2 complex. It is hypothesized that LPS binds to LptC at the IM, transfers to LptA to cross the periplasm, and is inserted by LptDE into the outer leaflet of the outer membrane. The studies described here comprehensively characterize and quantitate the binding of LPS to LptC. Site‐directed spin labeling electron paramagnetic resonance spectroscopy was utilized to characterize the LptC dimer in solution and monitor spin label mobility changes at 10 sites across the protein upon addition of exogenous LPS. The results indicate that soluble LptC forms concentration‐independent N‐terminal dimers in solution, LptA binding does not change the conformation of the LptC dimer nor appreciably disrupt the LptC dimer in vitro, and LPS binding affects the entire LptC protein, with the center and C‐terminal regions showing a greater affinity for LPS than the N‐terminal domain, which has similar dissociation constants to LptA.
The role of distance in the peer-to-peer market for tourist accommodation

This article provides evidence on the concentration of peer-to-peer tourist accommodations in the center of cities and the role of distance. On that basis, an explanatory model is proposed to understand the locating decisions of the different agents involved. The model is empirically implemented through a two-stage least squares regression, which allows estimating the elasticity of demand with respect to price and distance. Results for the Spanish cities of Barcelona and Madrid confirm similar price elasticity of demand in both (2.2 and 2.4, respectively) but greater sensibility of demand with respect to distance to the center in the former.
Tooth-specific and person-level predictors of 24-month tooth loss among older adults.

OBJECTIVES To describe: (1) the 24-month incidence of tooth loss in a diverse sample of dentate adults; and (2) the clinical, attitudinal, behavioral, and sociodemographic correlates of tooth loss incidence. METHODS The Florida Dental Care Study is a prospective longitudinal cohort study of persons who at baseline had at least one tooth, were 45 years or older, and who resided in north Florida. An in-person interview and clinical examination were conducted at baseline and 24-months after baseline, with 6-monthly telephone interviews between those times. A two-level hierarchical generalized linear regression (logit model) was used to quantify tooth-specific and person-level factors simultaneously. RESULTS Of the 739 persons who attended for a 24-month examination, 24% lost one or more teeth during follow-up. Tooth loss was more common in persons with dental disease at baseline, incident dental signs or symptoms, those with negative attitudes toward dental care and dental health, those with limited financial resources, older adults, blacks, females, and problem-oriented users of dental care (as distinct from regular attenders). Although disease presence at baseline was a major factor associated with incident tooth loss, most diseased teeth were in fact still present 24 months after baseline. CONCLUSIONS Other than periodontal attachment loss, severe tooth mobility, and dental caries, no single factor was a dominant predictor of tooth loss; instead, numerous factors made statistically significant but small contributions to variation in tooth loss. Tooth loss apparently is the result of complex interactions among dental disease, incident dental signs and symptoms, tendency to use dental care in response to specific dental problems, dental attitudes, and ability to afford non-extraction treatment alternatives.
Genetic structure of Camellia japonica L. in an old‐growth evergreen forest, Tsushima, Japan

The spatial genetic structure of Camellia japonica was investigated, using microsatellite markers, in a 4‐ha permanent plot within an old‐growth forest. Spatial distribution of individuals was also assessed to obtain an insight into spatial relationships between individuals and alleles. Morisita’s index of dispersion showed that 518 C. japonica individuals in the plot were clumped, and Moran’s I spatial autocorrelation coefficient revealed weak genetic structure, indicating a low level of allele clustering. Average I correlograms showed that there was stronger genetic structure over short‐distance classes. The clumped distribution of individuals and the positive autocorrelation over short‐distance classes may result from the limited seed dispersal and microsite heterogeneity of the stand, while the genetic structure may be weakened by overlapping seed shadow and extensive pollen flow, mediated by animal vectors, and the high outcrossing rate found in C. japonica.
Effect of age on cardiovascular responses to static muscular contraction in beagles.

Induced muscular contraction in anesthetized animals results in significant hemodynamic and regional blood flow (RBF) changes. Although reflex cardiovascular responses initiated in contracting muscle have been firmly established, little is known about the effects of age on these responses. Because other reflex responses that involve sympathetic activation appear to be attenuated with age, it was hypothesized that reflex efferent cardiovascular responses that normally occur during muscular contraction would be impaired in senescent dogs. Therefore, hemodynamic and RBF responses to induced static hindlimb contraction (HLC) were evaluated in 8- to 14- and 2- to 3-yr-old beagles during alpha-chloralose anesthesia. Most baseline hemodynamic parameters were similar in both groups, but heart rate was significantly (P < 0.05) higher in old dogs. During HLC, heart rate and blood pressure increased in the young and old dogs. However, increases in stroke volume and cardiac output were greater in old dogs, combined with a reduction in systemic vascular resistance not observed in young dogs. No age-related difference in baseline RBF (microspheres) was observed in six of eight abdominal regional circulations and in each of four skeletal muscle groups. During HLC, RBF reductions occurred in six of eight abdominal organs in young and old dogs. However, the reduction in RBF and concomitant increase in vascular resistance in all eight abdominal regions combined was almost twice as great in young vs. old dogs. In noncontracting skeletal muscle, RBF decreased and vascular resistance increased four times more in young vs. old dogs. (ABSTRACT TRUNCATED AT 250 WORDS)
Recent advances and novel treatment paradigms in acute lymphocytic leukemia

This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells. CAR T cells have demonstrated promising results in the relapsed/refractory setting. However, the use of BiTEs and CAR T cells is also associated with a distinct set of adverse reactions that must be taken into account by the treating physician. Apart from the above strategies, the use of other targeted therapies has attracted interest. Namely, the discovery of the Philadelphia (Ph)-like signature in children and young adults with ALL has led to the use of tyrosine kinase inhibitors (TKI) in these patients. The different drugs and strategies that are being tested in the relapsed/refractory ALL setting pose a unique challenge in identifying the optimum sequence of treatment and determining which approaches should be considered for frontline treatment.
Multiple Subcritical Arterial Stenoses: Effect on Postastenotic Pressure and Flow

Diminished poststenotic pressure and flow accompanied experimental application of multiple subcritical arterial stenoses in series. Effects of additional stenoses, causing equivalent constrictions, were cumulative in a nonlinear fashion. Seven-hundred-twenty measurements were performed using 10 cm ileofemoral canine arterial segments in vitro and in vivo with pulsatile and nonpulsatile blood flow. Pressures and flow volumes utilized for testing were within normal physiologic ranges. Data analysis included correlations of experimental observations with predictions generated from a theoretic hydraulic model. Kinetic energy losses with multiple subcritical stenoses were associated with decreased pressure and flow. Poststenotic pressure decreased as much as 51% in some experiments. Diminutions in flow paralleled pressure changes. Measured pressure changes were nonlinear and followed mathematic predictions of appreciable but lesser effects of added stenoses. Hemodynamic alterations of magnitudes documented in this study assume clinical importance. The assumption that a solitary critical stenosis must exist before significant hemodynamic changes occur is no longer tenable.
The immunosuppressive signature of menstrual blood mesenchymal stem cells entails opposite effects on experimental arthritis and graft versus host diseases

Recently, a noninvasive and highly proliferative stem cell population from menstrual blood called MenSCs has been identified. Despite their use in clinical studies, their immunomodulatory properties have not yet been investigated. In this context, we studied the immunosuppressive properties of MenSCs in comparison with the well‐characterized bone marrow derived‐MSCs (BM‐MSCs). Using an in vitro proliferation assays, we showed that MenSCs displayed a lower suppressive effect on peripheral blood mononuclear cells and in particular on the proinflammatory CD4+IFN‐γ+ and CD8+IFNγ+ cells than BM‐MSCs. Moreover, compared to BM‐MSCs, MenSCs activated with IFN‐γ and IL‐1β produced lower amounts of immunosuppressive factors such as IDO, PDL‐1, PGE2, and Activin A and exhibited a substantial lower expression level of IFN‐γ receptor subunits. In the collagen induced arthritis model, while BM‐MSCs administration resulted in a potent therapeutic effect associated with a significant decrease of proinflammatory T cell frequency in the lymph nodes, MenSCs injection did not. In contrast, in the xeno‐GVHD model, only MenSCs administration significantly increased the survival of mice. This beneficial effect mediated by MenSCs was associated with a higher capacity to migrate into the intestine and liver and not to their anti‐inflammatory capacities. All together our results demonstrate for the first time that the therapeutic potential of MSC in the experimental xeno‐GVHD model is independent of their immunosuppressive properties. These findings should be taken into consideration for the development of safe and effective cell therapies. Stem Cells 2016;34:456–469
Evaluating urban residents’ attitudes towards tourism development in Belgrade (Serbia)

ABSTRACT This study empirically examines the relationships among residents’ place image, various domains of tourism impacts, and residents’ support for tourism development in an Eastern European city, as well as the role of residents’ socio-demographic characteristics and place attachment. The direct, indirect, and moderating effects were investigated using structural equation modelling and the method suggested by Hayes and Preacher [2010. Estimating and testing indirect effects in simple mediation models when the constituent paths are nonlinear. Multivariate Behavioral Research, 45, 627–660]. The findings show that none of the tourism impacts mediate the relationship between place image and residents’ support for tourism development. Moreover, with respect to Belgrade, perceived economic impacts have the strongest effect on residents’ support, followed by perceived socio-cultural impacts. By assessing the respective contribution of the three tourism impacts simultaneously, the results highlight the weight residents assign to a city’s peculiarities, thus illustrating contextual influences such as post-communist and centrally planned economy legacies.
Potential Determinants of Drink Driving in Young Adults

Objective: The main purposes of this study were to examine the usefulness of the variables of the theory of planned behavior (viz. attitudes, social norms, and self-efficacy) and to explore the relationship between optimism bias and drink driving in young adults. In addition, we explored gender differences in drink driving with provision for the effect of variables such as driving frequency and alcohol consumption. Methods: Data were collected via a questionnaire administered to 274 drivers (59.9% females) aged 18–30 years (24.36 ± 2.96). Results: The results obtained with provision for driving frequency revealed substantial differences in driving behaviors between genders. Thus, males were more prone to drink driving, perceived less disapproval by their significant others (parents and peers), and felt less able to avoid drinking-and-driving situations. In addition, they self-reported more frequent alcohol consumption and driving under the influence. The results also confirm the significance of peers’ subjective norms and attitudes to drink driving in males. Overconfidence in their own driving skills for driving drunk and perceived behavioral control were found to be significant predictors for drink driving in females. Optimism bias also played a slightly significant role in predicting drink driving but only in females. Conclusions: The important practical implications of these results with a view to designing effective interventions to prevent the risks associated with drink driving in the young population are discussed. Interventions should focus on young people's perceptions of group norms and promoting cautionary driving choices and alternatives to drink driving.