Miracle-dz/UniFAR-FTUs huggingface dataset:
Lymphocyte‐Selective Cytostatic and Immunosuppressive Effects of Mycophenolic Acid in Vitro: Role of Deoxyguanosine Nucleotide Depletion

Mycophenolic acid (MPA), an inhibitor of inosine monophosphate dehydrogenase, in nanomolar concentrations blocks proliferative responses of cultured human, mouse and rat T lymphocytes and B lymphocytes to mitogens or in mixed lymphocyte reactions. The inhibitory effect of MPA on lymphocyte proliferation is reversed by addition to culture media of deoxyguanosine or guanosine but not by addition of deoxyadenosine or adenosine. The findings suggest that the principal mechanism of action of low concentrations of MPA is depletion of deoxyguanosine triphosphate which is required for DNA synthesis. In immunosuppressive doses, MPA does not affect the formation of IL‐1 by LPS‐activated human peripheral blood monocytes. Unlike cyclosporin A and FK‐506, MPA does not inhibit the formation of IL‐2 and the expression of the IL‐2 receptor in mitogen‐activated human T lymphocytes. MPA suppresses mixed lymphocyte reactions when added 3 days after their initiation. These findings suggest that MPA does not inhibit early responses of T and B lymphocytes lo mitogenic or antigenic stimulation but blocks the cells at the time of DNA synthesis. The cytostatic effect of MPA is more potent on lymphocytes than on other cell types, such as fibroblasts and endothelial cells. MPA also inhibits antibody formation by polyclonally activated human B lymphocytes. MPA is an immunosuppressive agent reversibly inhibiting proliferation of T and B lymphocytes and antibody formation, with a profile of activity different from that of other immunosuppressive drugs. Human T and B lymphocytic and promonocytic cell lines are highly sensitive to the antiproliferative effects of MPA, whereas the erythroid precursor cell line K562 is less susceptible. The effect of MPA on cells of the monocyte‐macrophage lineage could exert long‐acting anti‐inflammatory activity. MPA or analogues may have therapeutic utility in diseases such as rheumatoid arthritis, for prevention of allograft rejection and in lymphocytic or monocytic leukaemias and lymphomas.
Seeing through the interface: poly(ε‐Caprolactone) surface modification of poly(glycerol‐co‐sebacic acid) membranes in adult porcine retinal explants

The purpose of this study was to investigate the adhesion properties and tissue reactions in an in vitro model of nanofabricated membranes emulating the vitreous cortex. Electrospinning was performed for either 5, 10 or 15 min to create various thicknesses of poly(ε‐caprolactone) (PCL) fibre mats on a poly(glycerol‐co‐sebacic acid) (PGS) surface. These were fused with adult porcine retinal explants, with the fibre side facing the inner retina, and cultured for 5 days. Adherence was assessed by macroscopic inspection, and morphological and immunohistochemical analysis was performed using haematoxylin and eosin (H&E) and markers for photoreceptors and Müller glia (recoverin, NeuN, vimentin and GFAP). TUNEL labelling was performed to assess apoptosis. Five minute specimens displayed poor adherence with an overall structure, apoptosis and photoreceptor and ganglion cell morphology comparable to that of the culture controls, whereas 10 min specimens showed improved neuronal survival; 15 min composite explants adhered only at focal points, were thin and showed extensive degenerative damage. The physical composition of nanofibre meshes is important for adhesion to the inner retina and has a significant impact on neuronal and glial survival in vitro. The results bearing on research involving retinal transplantation are discussed. Copyright © 2016 John Wiley & Sons, Ltd.
Members of a Legionella pneumophila Family of Proteins with ExoU (Phospholipase A) Active Sites Are Translocated to Target Cells

ABSTRACT Legionella pneumophila replicates within alveolar macrophages, causing a severe pneumonia termed Legionnaires' disease. The bacterium resides within a vacuole that escapes immediate transport to the host lysosome. Instead, the vacuole interacts with the early secretory pathway to establish an environment suitable for rapid multiplication. A type IV secretion system is central to the pathogenicity of the bacterium, and many protein substrates that are translocated by this system to the host cell have been identified. One of these, VipD, was found to interrupt the late secretory pathway when overproduced in Saccharomyces cerevisiae. We independently identified VipD in a previous study and have further characterized this protein as well as its three paralogs. The vipD gene belongs to a family of L. pneumophila open reading frames that are predicted to contain a phospholipase A domain with sequence similarity to the type III-secreted toxin ExoU from Pseudomonas aeruginosa. Similarly to other known translocated proteins of L. pneumophila, VipD is strongly induced in early stationary phase, a time when the bacterium is most virulent. Detergent extraction studies of infected macrophages confirm that VipD is translocated into host cells via the type IV secretion system. A second assay for translocation revealed that two paralogs of VipD, VpdA and VpdB, also have translocation signals recognized by the type IV system. A strain lacking VipD and its three paralogs grew at wild-type rates in murine macrophages, although secondary mutations that cause growth defects in strains lacking VipD accumulate. The quadruple mutant displayed a growth advantage in the amoebal host Dictyostelium discoideum, indicating that the protein family may modulate intracellular growth in a complex fashion. VipD is mildly toxic when overproduced in eukaryotic cells, and the toxicity is partially dependent on the putative phospholipase active site. VipD and its paralogs therefore define a family of translocated proteins that may assist in the establishment of a vacuole suitable for bacterial replication through functioning as a phospholipase.
Cervical Cancer Screening in Tuscany: A Survey of the Actual State of Cervical Cancer Prevention in the Local Sanitary Units of the Tuscan Region

Every Local Sanitary Unit (USL) of the Tuscan Region was contacted to define screening variables, such as adequacy of the staff involved in prevention, smear technique, data collection and evaluation, laboratory quality control, and modalities of invitations to screening. The reported data show that 21 of 40 USL, but only 9 of 28 USL outside the Florence province (where a common screening program is performed), are performing active invitations to screening. The most serious staff inadequacies concern data evaluation and personnel performing the test. Sixteen of 28 USL outside Florence suggest an annual rescreening, which causes overcrowding of services and a poor availability for the unscreened population. Moreover, the poor quality of data collection makes it impossible to evaluate the benefit offered by the screening programs in the 28 USL outside Florence. Cytologic quality control is often lacking, and the smear technique is inadequate in 10 of 28 USL outside Florence. The lack in the USL of epidemiologic competence and of cost/benefit considerations and the need for political decisions about cancer prevention programs are stressed.
Osseointegrated Finger Prostheses

Amputation of a digit can lead to functional and psychological problems and patients can benefit from digital prostheses. Unfortunately, standard prostheses are often unstable, particularly when fitted over short amputation stumps. Prosthesis fixation by osseointegration is widely used in oral and extraoral applications and may help avoid the problem of instability. This paper reports the results of four patients with five finger amputations who were treated with osseointegrated implants to attach finger prostheses. One implant failed to osseointegrate and the procedure was abandoned. Three patients were successfully treated to completion of three finger prostheses and are extremely satisfied with their outcomes, both cosmetically and functionally, with osseoperception reported by all three patients.
Re-evaluating the link between brain size and behavioural ecology in primates

Comparative studies have identified a wide range of behavioural and ecological correlates of relative brain size, with results differing between taxonomic groups, and even within them. In primates for example, recent studies contradict one another over whether social or ecological factors are critical. A basic assumption of such studies is that with sufficiently large samples and appropriate analysis, robust correlations indicative of selection pressures on cognition will emerge. We carried out a comprehensive re-examination of correlates of primate brain size using two large comparative datasets and phylogenetic comparative methods. We found evidence in both datasets for associations between brain size and ecological variables (home range size, diet and activity period), but little evidence for an effect of social group size, a correlation which has previously formed the empirical basis of the Social Brain Hypothesis. However, reflecting divergent results in the literature, our results exhibited instability across datasets, even when they were matched for species composition and predictor variables. We identify several potential empirical and theoretical difficulties underlying this instability and suggest that these issues raise doubts about inferring cognitive selection pressures from behavioural correlates of brain size.
Growth and the Contribution of Changes in Export and Import Prices to Real Income Growth January 3 , 2013

Using recent data from the Bureau of Economic Analysis (BEA), the Bureau of Labour Statistics (BLS), the Board of Governors of the Federal Reserve System and the US Department of Agriculture, the paper uses a data set that covers the outputs produced and inputs used by an Extended Business Sector of the US economy for the years 1987-2011. The Extended Business Sector (EBS) consists of the entire US economy less the inputs used and outputs produced by the Public Administration sector and less the US housing sector. The study found that Multifactor Productivity (MFP) growth in the EBS averaged 1.157% per year, somewhat higher than BLS MFP growth in the Private Sector which averaged 0.962% per year. The study also produced estimates of MFP where a net output concept was used. Journal of Economic Literature Classification Numbers C43, C67, C82, D24, E22, E43. 1 School of Economics, University of British Columbia and School of Economics, University of New South Wales. The financial assistance of the SSHRC is gratefully acknowledged.
Diagnostic potential of hepcidin testing in pediatrics

Hepcidin, a peptide hormone released by hepatocytes into circulation is the main regulator of dietary iron absorption and cellular iron release. Although commercial tests are available, assay harmonization for hepcidin has not been yet reached, making reference intervals and consequent clinical decisions still elusive for each assay and specific population. The aim of this study is to set up hepcidin measurement in pediatric age and to investigate its potential usefulness in the diagnosis and management of iron disorders in children.
Finite rank Bratteli diagrams: Structure of invariant measures

We consider Bratteli diagrams of finite rank (not necessarily simple) and ergodic invariant measures with respect to the cofinal equivalence relation on their path spaces. It is shown that every ergodic invariant measure (finite or “regular” infinite) is obtained by an extension from a simple subdiagram. We further investigate quantitative properties of these measures, which are mainly determined by the asymptotic behavior of products of incidence matrices. A number of sufficient conditions for unique ergodicity are obtained. One of these is a condition of exact finite rank, which parallels a similar notion in measurable dynamics. Several examples illustrate the broad range of possible behavior of finite type diagrams and invariant measures on them. We then prove that the Vershik map on the path space of an exact finite rank diagram cannot be strongly mixing, independent of the ordering. On the other hand, for the so-called “consecutive” ordering, the Vershik map is not strongly mixing on all finite rank diagrams. MSC: 37B05, 37A25, 37A20.
Radionuclide assessment of left ventricular function in patients with mycardial infarction and diabetes mellitus

Abstract. The aim of this study was to compare left ventricular function, assessed by radionuclide angiocardiography, in 54 diabetics and 194 non‐diabetics with acute myocardial infarction (AMI). The most meaningful results concern the inferior AMI group, whose left ventricular ejection fraction (LVEF) and regional wall motion were significantly lower in diabetics than in non‐diabetics (LVEF was 44.2 ± 11 vs. 51.6 ± 9%, P < 0.005; the regional wall motion score was 0.46 ± 1 vs. 1.56 ± 1, P < 0.01, respectively), while no significant difference was observed in the anterior AMI group. However, in the group as a whole, the LVEF was 41 ± 13% in diabetics and 47 ± 13% in non‐diabetics (P < 0.01), the number of abnormally contracting segments was 2.0 ± 0.9 and 1.5 ± 1, respectively, and the wall motion score was 0.2 ± 1.1 and 1.0 ± 1.4, respectively (P < 0.01). These data could be explained by an underlying cardiac dysfunction in diabetes, in addition to AMI. The more marked difference between diabetics and non‐diabetics in inferior AMI might be related to the smaller infarct size in this group.
Pharmacokinetics of warfarin in the nephrotic syndrome and effect on vitamin K-dependent clotting factors.

The behavior of warfarin, a drug tightly bound to albumin, was studied in patients with nephrotic syndrome (NS) to assess the influence of hypoalbuminemia on its pharmacokinetics and its effect on vitamin K-dependent coagulation factors. A single dose of warfarin (8 mg) was given orally to 11 nephrotic patients with normal or nearly normal renal function and to 11 controls. In every subject the following measurements were performed: albuminemia before (t0) warfarin administration; plasma warfarin and vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) levels, before and at time intervals from 0 to 48 h after drug administration; warfarin urinary excretion from 0 to 24 h. Urinary warfarin excretion was null in 19 out of the 22 subjects and very low in two nephrotic patients and in one control. Low serum albumin in NS patients induced a twofold increase of unbound warfarin vs controls (3.5% vs 1.8%, p less than 0.001) which led to a threefold increase in plasma clearance of warfarin (9.70 vs 3.26 ml X min-1, p less than 0.001); as warfarin distribution volume showed only a slight (non significant) increase in NS patients, the elimination half-life was thus markedly shortened in NS patients vs controls (18 vs 36 h, p less than 0.01). Maximum warfarin effect on vitamin K-dependent factor levels occurred at 18 h in controls and 24 h in nephrotics, and these lowest values were similar, in spite of a higher level at 0 in NS patients. (ABSTRACT TRUNCATED AT 250 WORDS)
Factors Associated With Successful Chopart Amputation in Patients With Diabetes

Chopart amputations were first performed for treatment of a non-salvageable distal foot but became unfavorable because of the development of equinovarus contractures and ulcerations. The majority of below-knee amputations today occur in ambulatory patients with diabetes in which a Chopart amputation may be a viable option; however, the durability of the residual limb is questionable. The authors undertook a systematic review of electronic databases and other relevant sources to identify material relating to the factors associated with a successful Chopart amputation in ambulatory patients with diabetes. Studies were eligible for inclusion only if they consecutively enrolled ambulatory patients with diabetes who underwent a Chopart amputation, regardless of etiology, with or without any tendinous or osseous balancing performed and had a mean follow-up of ≥12 months duration. Four studies involving 74 patients/feet were identified that met the inclusion criteria with a weighted mean follow-up of 21.1 months. The efficacy of tendinous and/or osseous balancing could not be assessed because of the lack of comparable techniques. However, review of the included studies supports that a residual functional limb can be maintained for ≥12 months with the use of a properly fitting high-profile prosthetic device for lifelong ambulation.
Cross-referencing eukaryotic genomes: TIGR Orthologous Gene Alignments (TOGA).

Comparative genomics promises to rapidly accelerate the identification and functional classification of biologically important human genes. We developed the TIGR Orthologous Gene Alignment (TOGA; ) database to provide a cross-reference between fully and partially sequenced eukaryotic transcribed sequences. Starting with the assembled expressed sequence tag (EST) and gene sequences that comprise the 28 TIGR Gene Indices, we used high-stringency pair-wise sequence searches and a reflexive, transitive closure process to associate sequence-specific best hits, generating 32,652 tentative ortholog groups (TOGs). This has allowed us to identify putative orthologs and paralogs for known genes, as well as those that exist only as uncharacterized ESTs and to provide links to additional information including genome sequence and mapping data. TOGA provides an important new resource for the analysis of gene function in eukaryotes. In addition, an analysis of the most widely represented sequences can begin to provide insight into eukaryotic biological processes.
Damage type and strain mode associations in human compact bone bending fatigue

When compact bone is subjected to fatigue loading, it develops matrix microdamage, which reduces the tissue's ability to resist fracture. The relative influence of different strain modes on damage and strength in compact bone has not been characterized, to our knowledge. In this study, the nonuniform strain field produced by four‐point bending was used to introduce fatigue damage into tibial bending beam specimens from men 40‐49 years old. The specimens were then bulk‐stained with basic fuchsin to mark damage surfaces and were examined histologically and with confocal microscopy to describe damage morphologies and position relative to tension and compression‐strained regions of the specimen. Histomorphometric methods were used to quantify the amounts of different types of bone microdamage. Three major types were observed. In regions subjected to tensile strains, the bone had focal regions of diffusely increased basic fuchsin staining (i.e., diffuse microdamage). Confocal microscopy of these regions showed them to be composed of extensive networks of fine, ultrastructural‐level cracks. In compressive strain regions, the tissue developed linear microcracks in interstitial areas similar to those originally described by Frost. Fine, tearing‐type (wispyappearing) cracks were observed near and in the plane of the neutral axis. The paths of these fine cracks were not influenced by microstructural boundaries. Other minor damage morphologies (sector‐stained osteons, delamination of regions of lamellae, and intraosteonal cracking) were observed, but their distribution was unrelated to local strain field. Thus, in fatigue of human compact bone, the principal mechanisms of matrix failure (i.e., linear microcrack, diffuse damage foci, and tearing‐type damage) are strongly dependent on local strain type.
Effects of sex and proficiency in second language processing as revealed by a large‐scale fNIRS study of school‐aged children

Previous neuroimaging studies in adults have revealed that first and second languages (L1/L2) share similar neural substrates, and that proficiency is a major determinant of the neural organization of L2 in the lexical‐semantic and syntactic domains. However, little is known about neural substrates of children in the phonological domain, or about sex differences. Here, we conducted a large‐scale study (n = 484) of school‐aged children using functional near‐infrared spectroscopy and a word repetition task, which requires a great extent of phonological processing. We investigated cortical activation during word processing, emphasizing sex differences, to clarify similarities and differences between L1 and L2, and proficiency‐related differences during early L2 learning. L1 and L2 shared similar neural substrates with decreased activation in L2 compared to L1 in the posterior superior/middle temporal and angular/supramarginal gyri for both sexes. Significant sex differences were found in cortical activation within language areas during high‐frequency word but not during low‐frequency word processing. During high‐frequency word processing, widely distributed areas including the angular/supramarginal gyri were activated in boys, while more restricted areas, excluding the angular/supramarginal gyri were activated in girls. Significant sex differences were also found in L2 proficiency‐related activation: activation significantly increased with proficiency in boys, whereas no proficiency‐related differences were found in girls. Importantly, cortical sex differences emerged with proficiency. Based on previous research, the present results indicate that sex differences are acquired or enlarged during language development through different cognitive strategies between sexes, possibly reflecting their different memory functions. Hum Brain Mapp 36:3890–3911, 2015. © 2015 Wiley Periodicals, Inc.
Concurrent Inactivation of RB1 and TP53 Pathways in Anaplastic Oligodendrogliomas

Oligodendrogliomas are characterized by frequent loss of heterozygosity (LOH) on chromosomes 1p and 19q, but additional genetic alterations are likely to be involved. In this study, we screened 28 oligodendrogliomas (WHO grade II) and 20 anaplastic oligodendrogliomas (WHO grade III) for alterations in the RB1/CDK4/p16INK4a/p15INK4b and TP53/p14ARF/MDM2 pathways. In oligodendrogliomas, hypermethylation of RB1 (1 case) and p14ARF (6 cases) were the only detectable genetic changes (7/28, 25%). In anaplastic oligodendrogliomas, the RB1/CDK4/p16INK4a/p15INK4b signaling pathway regulating the G1 → S transition of the cell cycle was altered in 13/20 (65%) cases, by either RB1 alteration, CDK4 amplification, or p16INK4a/p15INK4b homozygous deletion or promoter hypermethylation. Further, 50% (10/20) of anaplastic oligodendrogliomas showed alterations in the TP53 pathway through promoter hypermethylation or homozygous deletion of the p14ARF gene and, less frequently, through TP53 mutation or MDM2 amplification. Of 13 anaplastic astrocytomas with an altered RB1 pathway, 9 (69%) also showed a dysregulated TP53 pathway. Thus, simultaneous disruption of the RB1/CDK4/p16INK4a/p15INK4b and the TP53/p14ARF/MDM2 pathways occurs in 45% (9/20) of anaplastic oligodendrogliomas, suggesting that these phenomena contribute to their malignant phenotype.