Miracle-dz/UniFAR-FTUs huggingface dataset:
LcrV is a channel size‐determining component of the Yop effector translocon of Yersinia

Delivery of Yop effector proteins by pathogenic Yersinia across the eukaryotic cell membrane requires LcrV, YopB and YopD. These proteins were also required for channel formation in infected erythrocytes and, using different osmolytes, the contact‐dependent haemolysis assay was used to study channel size. Channels associated with LcrV were around 3 nm, whereas the homologous PcrV protein of Pseudomonas aeruginosa induced channels of around 2 nm in diameter. In lipid bilayer membranes, purified LcrV and PcrV induced a stepwise conductance increase of 3 nS and 1 nS, respectively, in 1 M KCl. The regions important for channel size were localized to amino acids 127–195 of LcrV and to amino acids 106–173 of PcrV. The size of the channel correlated with the ability to translocate Yop effectors into host cells. We suggest that LcrV is a size‐determining structural component of the Yop translocon.
Witchcraft in early modern Europe: State-building and witch hunting in early modern Europe

During the last two decades a number of historians have attempted to establish a causal relationship between the great European witch hunt of the sixteenth and seventeenth centuries and the development of the modern state. These scholars have claimed that ‘the rise of the nationstate’ is at the very least one of the secondary causes of the witch hunt; that the hunt resulted from the centralisation of royal power; that it is one reflection of the advance of public authority against ‘particularism’ that it is integrally related to the assertion of reason of state; and that it proceeds from an impulse towards both absolutism and state sovereignty. The general impression one gets from this line of argument is that witches were in a certain sense victims of the advance of that emerging leviathan, the centralised, bureaucratised, secularised modern state. The purpose of this chapter is to examine this line of argument and to suggest some limitations to it. It will also test some of these theories about the connection between state-building and witch hunting with reference to one country in which it is alleged that they are especially apparent, the kingdom of Scotland. The argument consists of four separate but related strands. The first deals with judicial and administrative centralisation, which is incontestably one of the most salient features of state development. Here the argument is that the growth of the state involved the advance of central, i.e. royal, jurisdiction, as a result of which areas which had enjoyed a large measure of autonomy, especially those on the geographical periphery of royal domains, came within the ambit of central government control.
Chemokines and their receptors in rheumatoid arthritis: future targets?

Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction (1). In RA, migration of leukocytes into the synovial tissue (ST) occurs. These leukocytes and other cells in the ST, particularly RA ST fibroblasts, produce mediators of inflammation, including chemokines (1). Chemokines, currently numbering more than 50, are chemotactic cytokines that are important in recruitment of leukocytes and angiogenesis. They exert chemotactic activity toward a variety of cell types (2–7). Some chemokines, particularly CXC chemokines containing the ELR motif, are angiogenic. The last few years have seen a rapid development of studies aimed at targeting proinflammatory chemokines or their receptors in RA and animal models of RA (8,9). This review summarizes many of the important developments in this field. Based on the number of recently published studies, it is likely that the next few years will bring several new preclinical and clinical trials targeting chemokines.
Efficacy of school-based interventions aimed at decreasing sugar-sweetened beverage consumption among adolescents: a systematic review

Abstract Objective To verify the efficacy of school-based interventions aimed at reducing sugar-sweetened beverage (SSB) consumption among adolescents in order to develop or improve public health interventions. Design Systematic review of interventions targeting adolescents and/or the school environment. Setting The following databases were investigated: MEDLINE/PubMed, PsycINFO, CINAHL and EMBASE. Proquest Dissertations and Theses was also investigated for unpublished trials. Subjects Adolescents were defined as individuals between the ages of 12 and 17 years. Results A total of thirty-six studies detailing thirty-six different interventions tested among independent samples (n 152 001) were included in the review. Twenty interventions were classified as educational/behavioural and ten were classified as legislative/environmental interventions. Only six interventions targeted both individuals and their environment. Over 70 % of all interventions, regardless of whether they targeted individuals, their environment or both, were effective in decreasing SSB consumption. Legislative/environmental studies had the highest success rate (90·0 %). Educational/behavioural interventions only and interventions that combined educational/behavioural and legislative/environmental approaches were almost equally effective in reducing SSB consumption with success rates of 65·0 and 66·7 %, respectively. Among the interventions that had an educational/behavioural component, 61·5 % were theory-based. The behaviour change techniques most frequently used in interventions were providing information about the health consequences of performing the behaviour (72·2 %), restructuring the physical environment (47·2 %), behavioural goal setting (36·1 %), self-monitoring of behaviour (33·3 %), threat to health (30·6 %) and providing general social support (30·6 %). Conclusions School-based interventions show promising results to reduce SSB consumption among adolescents. A number of recommendations are made to improve future studies.
Sexually dimorphic link between dopamine D2 receptor gene and neuroticism-anxiety

Prior theory-driven research probing the association between dopaminergic candidate genes and human personality has focused on the trait of novelty seeking. Here, we examined the association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and two other personality traits, neuroticism-anxiety and agentic extraversion. We found no significant associations for agentic extraversion. However, for men, but not for women, we observed a strong and specific association between low neuroticism-anxiety and the A1+ allele of the DRD2 TaqI A polymorphism across two independent samples and across two alternative personality scales. We conclude that new theoretical models are needed to account for these and other recent reports of associations between neuroticism-anxiety and brain dopamine, which cannot be interpreted within the traditional framework.
Characterization of Molecular Mechanisms Underlying Mutations in Dystrophic Epidermolysis Bullosa Using Site-directed Mutagenesis*

Type VII collagen (C7) is a major component of anchoring fibrils, structures that mediate epidermal-dermal adherence. Mutations in gene COL7A1 encoding for C7 cause dystrophic epidermolysis bullosa (DEB), a genetic mechano-bullous disease. The biological consequences of specific COL7A1 mutations and the molecular mechanisms leading to DEB clinical phenotypes are unknown. In an attempt to establish genotype-phenotype relationships, we generated four individual substitution mutations that have been associated with recessive DEB, G2049E, R2063W, G2569R, and G2575R, and purified the recombinant mutant proteins. All mutant proteins were synthesized and secreted as a 290-kDa mutant C7 α chain at levels similar to wild type C7. The G2569R and G2575R glycine substitution mutations resulted in mutant C7 with increased sensitivity to protease degradation and decreased ability to form trimers. Limited proteolytic digestion of mutant G2049E and R2063W proteins yielded aberrant fragments and a triple helix with reduced stability. These two mutations next to the 39-amino acid helical interruption hinge region caused local destabilization of the triple-helix that exposed an additional highly sensitive proteolytic site within the region of the mutation. Our functional studies demonstrated that C7 is a potent pro-motility matrix for skin human keratinocyte migration and that this activity resides within the triple helical domain. Furthermore, G2049E and R2063W mutations reduced the ability of C7 to support fibroblast adhesion and keratinocyte migration. We conclude that known recessive DEB C7 mutations perturb critical functions of the C7 molecule and likely contribute to the clinical phenotypes of DEB patients.
Rock Geo-Mechanical State Alteration upon Entry of a Mechanized Longwall Set of Equipment into Pre-Mining Break-Down Chamber

Rapid development of coal deep mining equipment and technology, that is connected with widespread introduction of high-performance longwall sets of equipment is accompanied with an increase of economic losses in case of its possible downtime. The analysis of dismantling experience in modern Russian mines has shown that in absolute majority of cases the actual duration of re-assembling with regard to a longwall set of equipment exceeds technologically required time five and more times. In addition to that, reassembling time significantly depends on successful formation of a break-down chamber. Review results of the most wide-spread methods for break-down chamber formation in case of coal veins’ underground development with the use of modern longwall sets of equipment are presented in the article. The numerical modeling method has been applied to have a clear view of the stress-strain state (SSS) of the coal-bearing rock solid mass in the vicinity of a break-down chamber. In the furtherance of the set goal, a finite-element model of rock solid mass in vicinity of a pre-driven break-down chamber was developed to estimate qualitative nature and SSS alteration rate. The received results of computer simulation reflect the SSS distribution pattern of a solid mass, which coincides with in situ studies and allows assumption on a line of further researches.
Ras-induced activation of Raf-1 is dependent on tyrosine phosphorylation

Although Rafs play a central role in signal transduction, the mechanism(s) by which they become activated is poorly understood. Raf-1 activation is dependent on the protein's ability to bind Ras, but Ras binding is insufficient to activate Raf-1 tyrosine phosphorylation to this Ras-induced activation, in the absence of an over-expressed tyrosine kinase. We demonstrate that Raf-1 purified form Sf9 cells coinfected with baculovirus Ras but not Src could be inactivated by protein tyrosine phosphatase PTP-1B. 14-3-3 and Hsp90 proteins blocked both the tyrosine dephosphorylation and inactivation of Raf-1, suggesting that Raf-1 activity is phosphotyrosine dependent. In Ras-transformed NIH 3T3 cells, a minority of Raf-1 protein was membrane associated, but essentially all Raf-1 activity and Raf-1 phosphotyrosine fractionated with plasma membranes. Thus, the tyrosine-phosphorylated and active pool of Raf-1 constitute a membrane-localized subfraction which could also be inactivated with PTP-1B. By contrast, B-Raf has aspartic acid residues at positions homologous to those of the phosphorylated tyrosines (at 340 and 341) of Raf-1 and displays a high basal level of activity. B-Raf was not detectably tyrosine phosphorylated, membrane localized, or further activated upon Ras transformation, even though B-Raf has been shown to bind to Ras in vitro. We conclude that tyrosine phosphorylation is an essential component of the mechanism by which Ras activates Raf-1 kinase activity and that steady-state activated Ras is insufficient to activate B-Raf in vivo.
A deficit in the short-term retention of lexical-semantic information: forgetting words but remembering a story.

This article examines the long-term memory of a patient, AB, who had previously been reported to have problems in the short-term retention of word meanings. The authors found that AB had a problem not only in the short-term but also in the long-term retention of lexical-semantic information. AB, however, had no problem in the long-term retention of other kinds of information (pictures, shapes, propositional information). This pattern of results was interpreted as evidence that lexical-semantic representations have their own specific memory resources that are involved in the retention of the corresponding representations across different time intervals (e.g., they are involved in short-term as well as long-term retention). Implications for models of memory are discussed.
Inhibition of myoblast migration by prostacyclin is associated with enhanced cell fusion

Satellite cells are stem cells that are critical for the formation and growth of skeletal muscle during myogenesis. To differentiate and fuse, proliferating satellite cells or myoblasts must migrate and establish stable cell‐cell contacts. However, the factors that regulate myoblast migration and fusion are not understood completely. We have identified PGI2 as a novel regulator of myogenesis in vitro. PGI2 is a member of the family of prostaglandins (PG), autocrine/ paracrine signaling molecules synthesized via the cyclo‐oxygenase‐1 and ‐2 pathways. Primary mouse muscle cells both secrete PGI2 and express the PGI2 receptor, IP, at various stages of myogenesis. Using genetic and pharmacological approaches, we show that PGI2 is a negative regulator of myoblast migration that also enhances cell fusion. Thus, PGI2 may act as a “brake” on migrating cells to facilitate cell‐cell contact and fusion. Together, our results highlight the importance of the balance between positive and negative regulators in cell migration and myogenesis. This work may have implications for migration of other populations of adult stem cells and/or cells that undergo fusion. —Bondesen, B. A. , Jones, K. A. , Glasgow, W. C. , Pavlath, G. K. Inhibition of myoblast migration by prostacyclin is associated with enhanced cell fusion. FASEB J. 21, 3338–3345 (2007)
Promoting self-help strategies by sharing the lived experience of arthritis

Abstract A qualitative approach informed by the phenomenological concept of lived experience using semi-structured interviews explored the experience of living with arthritis. Audio-taped transcribed conversations were analysed using a computerassisted thematic analysis procedure. Strategies were offered for managing mornings, ensuring personal comfort, keeping a positive attitude, doing housework, cooking and meals, getting exercise, existing in day-to-day life, living at a slower pace, acknowledging feelings, dealing with depression, trying alternative treatments, accepting illness, getting sleep and rest, getting help, using help and handy gadgets, having emotional support, having determination, managing pain relief, using distractions, making adjustments, planning ahead, maintaining independence, having a social life, managing stress, adapting around young children, and facilitating self-awareness.
Prolonged Exposure of T Cells to TNF Down-Regulates TCRζ and Expression of the TCR/CD3 Complex at the Cell Surface1

A role for TNF-α in the pathogenesis of chronic inflammatory disease is now firmly established. Paradoxically, TNF also has potent immunomodulatory effects on CD4+ T lymphocytes, because Ag-specific proliferative and cytokine responses are suppressed following prolonged exposure to TNF. We explored whether TNF attenuated T cell activation by uncoupling proximal TCR signal transduction pathways using a mouse T cell hybridoma model. Chronic TNF exposure induced profound, but reversible, T cell hyporesponsiveness, with TNF-treated T cells requiring TCR engagement with higher peptide concentrations for longer periods of time for commitment to IL-2 production. Subsequent experiments revealed that chronic TNF exposure led to a reversible loss of TCRζ chain expression, in part through a reduction in gene transcription. Down-regulation of TCRζ expression impaired TCR/CD3 assembly and expression at the cell surface and uncoupled membrane-proximal tyrosine phosphorylation events, including phosphorylation of the TCRζ chain itself, CD3ε, ZAP-70 protein tyrosine kinase, and linker for activation of T cells (LAT). Intracellular Ca2+ mobilization was also suppressed in TNF-treated T cells. We propose that TNF may contribute to T cell hyporesponsiveness in chronic inflammatory and infectious diseases by mechanisms that include down-regulation of TCRζ expression. We speculate that by uncoupling proximal TCR signals TNF could also interrupt mechanisms of peripheral tolerance that are dependent upon intact TCR signal transduction pathways.
Looking for truth and finding lies: The prospects for a nascent neuroimaging of deception

Lying is ubiquitous and has acquired many names. In ‘natural experiments’, both pathological lying and truthfulness implicate prefrontal cortices. Recently, the advent of functional neuroimaging has allowed investigators to study deception in the non-pathological state. Prefrontal cortices are again implicated, although the regions identified vary across experiments. Forensic application of such technology (to the detection of deceit) requires the solution of tractable technical problems. Whether we ‘should’ detect deception remains an ethical problem: one for societies to resolve. However, such a procedure would only appear to be ethical when subjects volunteer to participate, as might occur during the investigation of alleged miscarriages of justice. We demonstrate how this might be approached.
Effect of gamma-ray radiation on physiological, morphological characters and chromosome aberrations of minitubers in Solanum tuberosum L.

Purpose: To investigate the effects of gamma-ray radiation on the physiological, morphological characters and chromosome aberrations of minitubers. Materials and methods: Minitubers of one potato cultivar, ‘Shepody’, were irradiated with 8 doses of gamma-rays (0, 10, 20, 30, 40, 50, 60, 70 and 80 Gy [Gray]) to investigate the effects of radiation on emergence ability, plant height and root length, morphological variations, chromosome aberrations, M1 (first generation mutants) tuber number and size of minituber plants. Results: Compared with the non-irradiated controls, the whole period of emergence was prolonged by 10–15 days for minitubers treated with gamma-ray radiation, but low doses of radiation (10, 20 and 30 Gy) promoted the emergence percentage of minitubers. With an increase in radiation dose, the emergence percentage, plant height and root length of minituber plants were significantly inhibited at 40 and 50 Gy. No emergence occurred at 60 Gy and higher doses. After radiation, a series of morphological variations and chromosome aberrations appeared in minituber plants. Radiation with 20 Gy promoted tuber formation, and the average number and diameter of M1 tubers per plant were significantly increased over the control by 71% and 34%, respectively. Conclusion: Low doses of radiation (10–30 Gy) might be used as a valuable parameter to study the improvement of minitubers by gamma-ray radiation treatment.
Composite Regions of Feasibility for Certain Classes of Distance Constrained Network Location Problems

Distance constrained network location involves locating m new facilities on a transport network G so as to satisfy upper bounds on distances between pairs of new facilities and pairs of new and existing facilities. The problem is (N-script)(P-script)-complete in general, but polynomially solvable for certain classes. While it is possible to give a consistency characterization for these classes, it does not seem possible to give a global description of the feasible set. However, substantial geometrical insights can be obtained on the feasible set by studying its projections onto the network. The j -th projection defines the j -th composite region which is the set of all points in G at which new facility j can be feasibly placed without violating consistency. We give efficient methods to construct these regions for solvable classes without having to know the feasible set and discuss implications on consistency characterization, what if analysis, and recursive solution constructions.
Treatment of Guillain‐Barré syndrome with high‐dose gammaglobulin

Intravenous gammaglobulin (IVGG) can improve the clinical course of several immune-mediated diseases. We report the first results of such treatment in eight patients with severe Guillain-Barré syndrome (GBS). We observed that IVGG was beneficial in at least some of the patients with severe GBS. These results should be confirmed in a randomized trial.
Six- and twelve-month outcomes among homeless youth accessing therapy and case management services through an urban drop-in center.

RESEARCH OBJECTIVE To evaluate the impact of case management and individual therapy offered through a drop-in center for homeless youth on substance use, mental health, housing, education, employment, and medical care utilization. STUDY POPULATION All youth (n=172) between the ages of 14-24 who accessed treatment services through an urban, southwestern drop-in center were included. DATA SOURCE Semistructured and self-report questionnaires were administered to youth between October 2002 and April 2005. STUDY DESIGN A repeated measures design was utilized. Youth were assessed at baseline, 6 months, and 12 months postbaseline. Hierarchical linear modeling was used to test the hypotheses. PRINCIPAL FINDINGS Statistically significant improvements were found in substance abuse, mental health, and percent days housed up to 12 months postbaseline. Decreased alcohol and drug use was associated with an increase in housing. However, most youth did not acquire permanent housing, and education, employment, and medical service utilization did not significantly change over time. CONCLUSIONS While treatment offered through drop-in centers for homeless youth can positively impact homeless youth, policy, funding, and service provision need greater focus, collaboration, and support if youth homelessness is to be successfully addressed.
Repair of Patellar Tendon Rupture Using Suture Anchors

Acute isolated rupture of the patellar tendon traditionally has been repaired via transpatellar suture tunnels. This retrospective study evaluated the demographics and epidemiology of this injury as well as the effectiveness and complication rates of our suture anchor technique. Between 1993 and 2005, a total of 82 cases of patellar tendon disruption in 71 patients were repaired. Fourteen cases involved basic primary repair with suture anchors of an acute isolated rupture of the patellar tendon and had an average follow-up of 29 months (range: 3-112 months). There were 3 (21%) failures of repair. The remaining 11 patients had excellent range of motion and strength and returned to their preoperative level of function. These results are comparable with other reports in the literature. The suture anchor technique thus represents a viable option for repair of patellar tendon ruptures and should be investigated further with a randomized, controlled trial.
KIR‐HLA Mismatching in Human Renal Allograft Transplantation: Emergence of a New Concept

The major immunological barrier to allograft survival is HLA incompatibility. Such alloantigenic differences between a donor and recipient provoke T and B lymphocyte responses, which will result in graft loss unless immunosuppressive drugs are administered. Natural Killer (NK) cells, another type of lymphocyte in the mononuclear cell compartment, have not typically been considered a threat to solid organ allograft survival. Historically, NK cells were thought of as components of innate immunity based on their intrinsic ability to spontaneously kill target cells independent of HLA antigen restriction. However, it is now clear that NK cells are quite sophisticated and use a highly specific and complex target cell recognition receptor system arbitrated via a multitude of inhibitory and activating receptors (1).