Miracle-dz/UniFAR-FTUs huggingface dataset:
The HimA and HimD subunits of integration host factor can specifically bind to DNA as homodimers.

Integration host factor (IHF) is a heterodimeric protein from Escherichia coli which specifically binds to an asymmetric consensus sequence. We have isolated the individual subunits of IHF, HimA and HimD, and show that an active IHF protein can be reconstituted from these subunits. The HimA and HimD polypeptides alone are capable of specifically recognizing the same ihf sequence. The mobilities of the protein‐DNA complexes in a gel‐retardation assay suggest that the proteins bind as homodimers. The stability of the HimD‐DNA complex is approximately 100‐fold lower than that of the IHF‐DNA complex. The HimA‐DNA complex is even less stable and is only observed when a large excess of HimA is used. This instability is possibly due to the inability of HimA to form stable homodimers. By domain swapping between HimA and HimD, we have constructed an IHF fusion protein which has the putative DNA‐binding domains of only HimA. This fusion protein forms stable dimers and makes specific protein‐DNA complexes with a high efficiency. A comparable fusion protein with only the DNA‐binding domains of HimD forms less stable complexes, suggesting that sequence‐specific contacts between IHF and the ihf consensus are mainly provided by the HimA subunit.
Airway complications after covered stent placement for malignant esophageal stricture: special reference to radiation therapy.

OBJECTIVE The purpose of this study was to evaluate the characteristics of airway complications and survival with special reference to radiation therapy in the care of patients undergoing covered stent placement for malignant esophageal strictures. MATERIALS AND METHODS A total of 208 patients who underwent stent placement with or without palliative radiation therapy for inoperable esophageal cancer were included. The endpoints were frequency, type, and management of airway complications; association between occurrence of airway complications and radiation therapy history; and differences in stent-to-complication interval and survival period after esophageal stenting between patients who underwent radiation therapy before and those who underwent radiation therapy after stent placement. RESULTS Airway complications occurred in 23 patients (11.1%): 18 (78.3%) had esophagorespiratory fistula, three (13.0%) had airway narrowing, and two (8.7%) had both complications. The frequency of airway complications was significantly greater among patients who underwent RT than those who did not (p = 0.005) but was not significantly different between the radiation before stenting and radiation after stenting groups (p = 0.158). The median stent-to-complication interval and survival period after esophageal stenting were significantly shorter in the radiation before stenting group than in the radiation after stenting group (p = 0.002, p = 0.001). CONCLUSION Esophagorespiratory fistula is much more common than airway narrowing as an airway complication. The rate of complications increases significantly in association with radiation therapy among patients with malignant esophageal stricture. Clinicians need to be aware of earlier airway complications and poorer prognosis among patients who undergo radiation therapy before placement of an esophageal stent than in patients who undergo radiation after stent placement.
The Recruitment of Normal Healthy Volunteers: A Review of The Literature on the Use of Financial Incentives

Unresolved issues of ethical, methodological, and legal concerns in the use of normal healthy volunteers persist. Financial incentives in their recruitment offer a unique ethical dilemma because of questions surrounding payment. A review of literature was conducted to obtain research systematically examining volunteer motivation and the role of financial incentives. The primary selection criterion was motivation and payment to volunteers; seven studies met the criterion for re view. Studies that have systematically investigated volunteer motivation have found financial rewards to be an important motivator among normal healthy volunteers in their decision to participate in clinical trials. Also evident is that differences based on demographic characteristics exist in the motivation and rates of volunteerism. Ethical issues surrounding the use of normal healthy volunteers are discussed, with attention to the issue of financial incentives (e.g., economically vulnerable volunteers, undue inducements). Regulations, guidelines, and recommendations are discussed with regard to volunteers and financial incentives.
Folding and stability of helical bundle proteins from coarse‐grained models

We develop a coarse‐grained model where solvent is considered implicitly, electrostatics are included as short‐range interactions, and side‐chains are coarse‐grained to a single bead. The model depends on three main parameters: hydrophobic, electrostatic, and side‐chain hydrogen bond strength. The parameters are determined by considering three level of approximations and characterizing the folding for three selected proteins (training set). Nine additional proteins (containing up to 126 residues) as well as mutated versions (test set) are folded with the given parameters. In all folding simulations, the initial state is a random coil configuration. Besides the native state, some proteins fold into an additional state differing in the topology (structure of the helical bundle). We discuss the stability of the native states, and compare the dynamics of our model to all atom molecular dynamics simulations as well as some general properties on the interactions governing folding dynamics. Proteins 2013; 81:1200–1211. © 2013 Wiley Periodicals, Inc.
Enhanced lycopene production in Escherichia coli engineered to synthesize isopentenyl diphosphate and dimethylallyl diphosphate from mevalonate

To increase expression of lycopene synthetic genes crtE, crtB, crtI, and ipiHP1, the four exogenous genes were cloned into a high copy pTrc99A vector with a strong trc promoter. Recombinant Escherichia coli harboring pT‐LYCm4 produced 17 mg/L of lycopene. The mevalonate lower pathway, composed of mvaK1, mvaK2, mvaD, and idi, was engineered to produce pSSN12Didi for an efficient supply of the lycopene building blocks, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Mevalonate was supplied as a substrate for the mevalonate lower pathway. Lycopene production in E. coli harboring pT‐LYCm4 and pSSN12Didi with supplementation of 3.3 mM mevalonate was more than threefold greater than bacteria with pT‐LYCm4 only. Lycopene production was dependent on mevalonate concentration supplied in the culture. Clump formation was observed as cells accumulated more lycopene. Further clumping was prevented by adding the surfactant Tween 80 0.5% (w/v), which also increased lycopene production and cell growth. When recombinant E. coli harboring pT‐LYCm4 and pSSN12Didi was cultivated in 2YT medium containing 2% (w/v) glycerol as a carbon source, 6.6 mM mevalonate for the mevalonate lower pathway, and 0.5% (w/v) Tween 80 to prevent clump formation, lycopene production was 102 mg/L and 22 mg/g dry cell weight, and cell growth had an OD600 value of 15 for 72 h. © 2006 Wiley Periodicals, Inc.
ABT‐737 is a useful component of combinatory chemotherapies for chronic myeloid leukaemias with diverse drug‐resistance mechanisms

The effect of ABT‐737, a BH3‐mimicking inhibitor for anti‐apoptotic Bcl‐2 and Bcl‐XL, but not Mcl‐1, against Bcr‐Abl‐positive (Bcr‐Abl+) leukaemic cells was examined. ABT‐737 potently induced apoptosis in Bcr‐Abl+ chronic myeloid leukaemia (CML) cell lines and primary CML samples in vitro and prolonged the survival of mice xenografted with BV173 cells, a CML cell line. Higher expression of anti‐apoptotic Bcl‐2 proteins reduced cell killing by ABT‐737 in each cell line, but there was no correlation between the sensitivities to ABT‐737 and the specific expression patterns of Bcl‐2 family proteins among cell lines. Thus, the cell killing effect of ABT‐737 must be determined not only by the expression patterns of Bcl‐2 family proteins but also by other mechanisms, such as high expression of Bcr‐Abl, or a drug‐efflux pump, in CML cells. ABT‐737 augmented the cell killing effect of imatinib in Bcr‐Abl+ cells with diverse drug‐resistance mechanisms unless leukaemic cells harboured imatinib‐insensitive Abl kinase domain mutations, such as T315I. The combination of homoharringtonine that reduces Mcl‐1 enhanced the killing by ABT‐737 strongly in Bcr‐Abl+ cells even with T315I mutation. These results suggest that ABT‐737 is a useful component of chemotherapies for CML with diverse drug‐resistance mechanisms.
Characterization of Gastrin-Induced Proangiogenic Effects In vivo in Orthotopic U373 Experimental Human Glioblastomas and In vitro in Human Umbilical Vein Endothelial Cells

Purpose: This study aims to investigate the role of gastrin-17 (G17) on angiogenesis features in gliomas both in vitro and in vivo. Experimental Design: The influences of G17 and G17 receptor antagonists were characterized in vitro in terms of angiogenesis on human umbilical vein endothelial cell (HUVEC) tubulogenesis processes on Matrigel and in vivo with respect to U373 orthotopic glioma xenografts. The influence of phosphatidylinositol 3′-kinase, protein kinase C, and nuclear factor-κB inhibitors was characterized in vitro on G17-mediated HUVEC tubulogenesis. G17-mediated release of interleukin (IL)-8 from HUVECs and G17-induced modifications in nuclear factor-κB DNA binding activity were characterized by means of specific enzyme-linked immunosorbent assays. The influence of G17 on E- and P-selectin expression was determined by means of computer-assisted microscopy, whereas the influence of E- and P-selectin on HUVEC migration was approached by means of antisense oligonucleotides. The chemotactic influence of G17 and IL-8 on HUVEC migration was characterized by means of computer-assisted videomicroscopy with Dunn chambers. Results: Messenger RNAs for cholecystokinin (CCK)A, CCKB, and CCKC receptors were present in HUVECs and microvessels dissected from a human glioblastoma. Whereas G17 significantly increased the levels of angiogenesis in vivo in the U373 experimental glioma model and in vitro in the HUVECs, the CCKB receptor antagonist L365,260 significantly counteracted the G17-mediated proangiogenic effects. G17 chemoattracted HUVECs, whereas IL-8 failed to do so. IL-8 receptor α (CXCR1) and IL-8 receptor β (CXCR2) mRNAs were not detected in these endothelial cells. Gastrin significantly (but only transiently) decreased the level of expression of E-selectin, but not P-selectin, whereas IL-8 increased the expression of E-selectin. Specific antisense oligonucleotides against E- and P-selectin significantly decreased HUVEC tubulogenesis processes in vitro on Matrigel. Conclusions: The present study shows that gastrin has marked proangiogenic effects in vivo on experimental gliomas and in vitro on HUVECs. This effect depends in part on the level of E-selectin activation, but not on IL-8 expression/release by HUVECs.
Assessment of Ankylosing Spondylitis Criteria in Patients with Chronic Low Back Pain and Vertebral Endplate Modic I Signal Changes

Objective. Patients with chronic low back pain (cLBP) and vertebral endplate Modic I signal changes on lumbar magnetic resonance imaging (MRI) have clinical features that could mimic inflammatory back pain related to spondyloarthritis (SpA) and/or ankylosing spondylitis (AS). We aimed to assess whether such patients fulfilled criteria for SpA and/or AS. Methods. For 5 months in 2008, all patients (n = 314) referred to a tertiary care physical medicine and rehabilitation facility in France were consecutively screened. A total of 185 hospitalized for non-specific cLBP were prospectively assessed. Forty patients fulfilling inclusion criteria were consecutively enrolled and included in 2 groups according to MRI findings: Modic I (n = 15) and non-Modic I (n = 25). MRI findings were assessed independently by 2 spine specialists and a radiologist. HLA-B27 status was determined. Data were collected on clinical measurements and fulfillment of Amor criteria (AC) and modified New York criteria (mNYC). All assessors were blinded to HLA-B27 status. Results. Whatever the Modic group, no patient fulfilled AC or mNYC, and mean total scores were comparable [3 ± 2 (range 0–22; p = 0.977), 1 ± 1 (range 0–3; p = 1.000), and 0 ± 0 (range 0–1; p = 1.000) for AC and clinical and radiological mNYC, respectively]. HLA-B27 status was similar in both groups [n = 2 (13%) vs n = 0 (0%); p = 0.135]. Conclusion. Patients with cLBP and Modic I vertebral endplate signal changes on lumbar MRI do not fulfill widely used and validated criteria for SpA and/or AS. Such cases are clinically distinct from SpA and AS.
Anaemia and low body mass index are associated with increased cardiovascular disease in patients with Takayasu arteritis.

OBJECTIVES Despite the high prevalence of cardiovascular disease (CVD) among patients with Takayasu arteritis (TA), few studies have identified its clinical correlates. The aim of this study was to analyse the prevalence of CVD and its association with traditional CV risk factors and disease-related variables in patients with TA. METHODS A total of 262 consecutive patients with a diagnosis of TA between January 2009 and July 2013 were included in this study. The primary outcome was CVD, defined as the presence of a previous history of myocardial infarction, angina, coronary disease, coronary bypass surgery, coronary angioplasty, and stroke. Multivariate logistic regression analysis was used to determine the relationship of conventional CV risk factors and TA-related variables to the presence of CVD. RESULTS CVD was present in 64 (24.4%) of patients with TA. Of the total cohort, 16 (6.1%) had a history of myocardial infarction, 31 (11.8%) had angina and 24 (9.2%) had stroke. Multivariate logistic regression analysis revealed that anaemia (OR, 2.449; 95% CI: 1.167-5.141, p=0.018), low body mass index (OR, 0.821; 95% CI: 0.723-0.932, p=0.002), advancing age (OR, 1.050; 95% CI: 1.013-1.088, p=0.007), hyperlipidaemia (OR, 3.792; 95% CI: 1.647-8.727, p=0.002), and family history of CVD (OR, 2.915; 95% CI: 1.188-7.153, p=0.019) were significantly associated with the presence of CVD. CONCLUSIONS Our study suggests that in addition to traditional CV risk factors, anaemia and low body mass index are independently associated with increased CVD in patients with TA.
Coffee consumption and the risk of primary liver cancer: Pooled analysis of two prospective studies in Japan

Although case‐control studies suggested that coffee consumption is associated with a decreased risk of liver cancer, no prospective cohort study has been carried out. To examine the association between coffee consumption and the risk of liver cancer, we conducted a pooled analysis of data available from 2 cohort studies in Japan. A self‐administered questionnaire about the frequency of coffee consumption and other health habits was distributed to 22,404 subjects (10,588 men and 11,816 women) in Cohort 1 and 38,703 subjects (18,869 men and 19,834 women) in Cohort 2, aged 40 years or more, with no previous history of cancer. We identified 70 and 47 cases of liver cancer among the subjects in Cohort 1 (9 years of follow‐up with 170,640 person‐years) and Cohort 2 (7 years of follow‐up with 284,948 person‐years), respectively. We used Cox proportional hazards regression analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of liver cancer incidence. After adjustment for potential confounders, the pooled RR (95% CI) of drinking coffee never, occasionally and 1 or more cups/day were 1.00 (Reference), 0.71 (0.46–1.09) and 0.58 (0.36–0.96), respectively (p for trend = 0.024). In the subgroup of subjects with a history of liver disease, we found a significant inverse association between coffee consumption and the risk of liver cancer. Our findings support the hypothesis that coffee consumption decreases the risk of liver cancer. Further studies to investigate the role of coffee in prevention of liver cancer among the high‐risk population are needed. © 2005 Wiley‐Liss, Inc.
Methane production and microbial protein synthesis in adult sheep fed total mixed ration as mash and as complete feed block

Abstract Sixteen rams in two groups were fed ad libitum total mixed ration as mash (TMRm) and as block (TMRb) for 90 days, and methane (CH4) emission was estimated by standard SF6 tracer technique. Feed samples were also incubated in vitro for calculating CH4 emission. In vitro incubation revealed lower (P < 0.05) gas production and CH4 from TMRb. Rams fed on TMRb consumed higher (P < 0.05) dry matter (DM), digestible crude protein (CP) and metabolizable energy (ME). The digestibility of nutrients was similar between the groups except for CP, which was higher in TMRb. The CH4 emission per unit digestible DM and organic matter intake was lower (P < 0.05) from TMRb, resulting in lower energy loss as percentage of dietary energy and higher ME intake as compared to TMRm. Microbial protein synthesis (MPS) as assessed from urinary purine derivatives was higher in TMRb. The rams on TMRb also exhibited improved N utilization compared to TMRm. Post-feeding (4 h) ruminal attributes in TMRm showed higher total N and lower acetic and butyric acid with an increased total ciliate protozoa and entodinia population. It may be concluded that TMR offered in block form emits less CH4 and saves ME, besides improving CP digestibility, MPS and N utilization.
A fatal case of Ludwig's angina and mediastinitis caused by an unusual microorganism, Gemella morbillorum

We present a case of Ludwig's angina in a 48-y-old immunocompetent male caused by an unusual pathogen, Gemella morbillorum. The infection was complicated with mediastinitis and despite aggressive management of the disease the patient died after 12 d of hospitalization. This is the first reported case of Ludwig's angina caused by G. morbillorum and emphasizes that the disease remains a potentially lethal infection.
Impairments of movement kinematics in patients with Huntington's disease: A comparison with and without a concurrent task

This study aimed to quantify the efficiency and smoothness of voluntary movement in Huntington's disease (HD) by the use of a graphics tablet that permits analysis of movement profiles. In particular, we aimed to ascertain whether a concurrent task (digit span) would affect the kinematics of goal‐directed movements. Twelve patients with HD and their matched controls performed 12 vertical zig‐zag movements, with both left and right hands (with and without the concurrent task), to large or small circular targets over long or short extents. The concurrent task was associated with shorter movement times and reduced right‐hand superiority. Patients with HD were overall slower, especially with long strokes, and had similar peak velocities for both small and large targets, so that controls could better accommodate differences in target size. Patients with HD spent more time decelerating, especially with small targets, whereas controls allocated more nearly equal proportions of time to the acceleration and deceleration phases of movement, especially with large targets. Short strokes were generally less force inefficient than were long strokes, especially so for either hand in either group in the absence of the concurrent task, and for the right hand in its presence. With the concurrent task, however, the left hand's behavior changed differentially for the two groups; for patients with HD, it became more force efficient with short strokes and even less efficient with long strokes, whereas for controls, it became more efficient with long strokes. Controls may be able to divert attention away from the inferior left hand, increasing its automaticity, whereas patients with HD, because of disease, may be forced to engage even further online visual control under the demands of a concurrent task. Patients with HD may perhaps become increasingly reliant on terminal visual guidance, which indicates an impairment in constructing and refining an internal representation of the movement necessary for its effective execution. Basal ganglia dysfunction may impair the ability to use internally generated cues to guide movement.
Antifungal activity of Juniperus essential oils against dermatophyte, Aspergillus and Candida strains

Aims: The increasing resistance to antifungal compounds and the reduced number of available drugs led us to search therapeutic alternatives among aromatic plants and their essential oils, empirically used by antifungal proprieties. In this work the authors report on the antifungal activity of Juniperus essential oils (Juniperus communis ssp. alpina, J. oxycedrus ssp. oxycedrus and J. turbinata).
Vpr Protein of Human Immunodeficiency Virus Type 1 Binds to 14-3-3 Proteins and Facilitates Complex Formation with Cdc25C: Implications for Cell Cycle Arrest

ABSTRACT Vpr and selected mutants were used in a Saccharomyces cerevisiae two-hybrid screen to identify cellular interactors. We found Vpr interacted with 14-3-3 proteins, a family regulating a multitude of proteins in the cell. Vpr mutant R80A, which is inactive in cell cycle arrest, did not interact with 14-3-3. 14-3-3 proteins regulate the G2/M transition by inactivating Cdc25C phosphatase via binding to the phosphorylated serine residue at position 216 of Cdc25C. 14-3-3 overexpression in human cells synergized with Vpr in the arrest of cell cycle. Vpr did not arrest efficiently cells not expressing 14-3-3σ. This indicated that a full complement of 14-3-3 proteins is necessary for optimal Vpr function on the cell cycle. Mutational analysis showed that the C-terminal portion of Vpr, known to harbor its cell cycle-arresting activity, bound directly to the C-terminal part of 14-3-3, outside of its phosphopeptide-binding pocket. Vpr expression shifted localization of the mutant Cdc25C S216A to the cytoplasm, indicating that Vpr promotes the association of 14-3-3 and Cdc25C, independently of the presence of serine 216. Immunoprecipitations of cell extracts indicated the presence of triple complexes (Vpr/14-3-3/Cdc25C). These results indicate that Vpr promotes cell cycle arrest at the G2/M phase by facilitating association of 14-3-3 and Cdc25C independently of the latter's phosphorylation status.
Effects on mortality and stress response in European sea bass, Dicentrarchus labrax (L.), fed mannan oligosaccharides (MOS) after Vibrio anguillarum exposure.

The effects of dietary mannan oligosaccharides (MOS; 4 g kg(-1) ; Bio-Mos, Alltech Inc, USA) in diets for European sea bass, Dicentrarchus labrax (L.), juveniles in relation to disease and stress resistance, combining intestinal infection with Vibrio anguillarum and stress challenge by confinement, were assessed in this study. After 8 weeks of MOS supplementation, fish were exposed to a pathogen challenge test against V. anguillarum by direct gut inoculation combined with a confinement stressor panel. Cumulative mortality of fish fed MOS caused by anally inoculated V. anguillarum decreased from 66% to 12.5% and from 54.1% to 25% in infected and infected + stressed fish, respectively, compared to fish fed control diet. Results for European sea bass revealed a positive effect of MOS dietary inclusion on disease resistance, in terms of cumulative mortality, against gut inoculated V. anguillarum, as well as reduced effects of stress on microbiota diversity. Both of these findings, together with the enhanced innate immune response and the higher gut mucus production and density of eosinophil granulocytes in gut mucosa obtained in previous studies after MOS supplementation (Torrecillas et al. 2007, 2011a,b) suggest that general reinforcement of the innate immune system, and particularly of the intestinal barrier efficiency, is the main defence mechanism of European sea bass fed MOS against pathogenic microorganisms.