Miracle-dz/UniFAR-FTUs huggingface dataset:
SYNTAX score is a predictor of angiographic no-reflow in patients with ST-elevation myocardial infarction treated with a primary percutaneous coronary intervention

ObjectivesThe no-reflow phenomenon has a negative prognostic value in patients with acute ST-elevation myocardial infarction (STEMI). The SYNTAX score (SS) quantifies the extent and complexity of angiographic disease and predicts long-term mortality and morbidity in STEMI. We aimed to assess the no-reflow and its possible relationships with SS and clinical characteristics in patients with STEMI treated with a primary percutaneous coronary intervention (PPCI). Materials and methodsIn this study, 880 patients with STEMI treated with PPCI were included prospectively (646 men and 234 women, mean age 58.5±12.4 years). The SS, thrombolysis in myocardial infarction (TIMI) flow grade score, and TIMI myocardial blush grade score were determined in all patients. No-reflow was defined as TIMI grade 0, 1 and 2 flows or TIMI grade 3 with myocardial blush grade 0 and 1. The patients were divided into two groups: a normal flow group and a no-reflow group. ResultsNo-reflow was observed in 32.8% of patients. The mean SS of the no-reflow group was higher than that of the normal flow group (19.2±6.8/12.9±6.1, P<0.001). On multivariate logistic regression analysis, SS [&bgr;=0.872, 95% confidence interval (CI)=0.845–0.899, P<0.001], diabetes (&bgr;=0.767, 95% CI=0.128–4.597, P=0.004), anterior myocardial infarction (&bgr;=5.421, 95% CI=1.369–21.469, P=0.025), and thrombus grade after wiring (&bgr;=2.537, 95% CI=1.506–4.273, P<0.001) were found to be independent predictors of no-reflow. The cutoff value of SS obtained by the receiver-operator characteristic curve analysis was 19.75 for the prediction of no-reflow (sensitivity: 70.6%, specificity: 69.4%). ConclusionThe SS is a predictor of no-reflow in patients with STEMI treated with PPCI.
Connexin 43 deficiency attenuates loss of trabecular bone and prevents suppression of cortical bone formation during unloading

Connexin 43 (Cx43) is the most abundant gap junction protein in bone and has been demonstrated as an integral component of skeletal homeostasis. In the present study, we sought to further refine the role of Cx43 in the response to mechanical unloading by subjecting skeletally mature mice with a bone‐specific deletion of Cx43 (cKO) to 3 weeks of mechanical unloading via hindlimb suspension (HLS). The HLS model was selected to recapitulate the effects of skeletal unloading due to prolonged bed rest, reduced activity associated with aging, and spaceflight microgravity. At baseline, the cortical bone of cKO mice displayed an osteopenic phenotype, with expanded cortices, decreased cortical thickness, decreased bone mineral density, and increased porosity. There was no baseline trabecular phenotype. After 3 weeks of HLS, wild‐type (WT) mice experienced a substantial decline in trabecular bone volume fraction, connectivity density, trabecular thickness, and trabecular tissue mineral density. These deleterious effects were attenuated in cKO mice. Conversely, there was a similar and significant amount of cortical bone loss in both WT and cKO. Interestingly, mechanical testing revealed a greater loss of strength and rigidity for cKO during HLS. Analysis of double‐label quantitative histomorphometry data demonstrated a substantial decrease in bone formation rate, mineralizing surface, and mineral apposition rate at both the periosteal and endocortical surfaces of the femur after unloading of WT mice. This suppression of bone formation was not observed in cKO mice, in which parameters were maintained at baseline levels. Taken together, the results of the present study indicate that Cx43 deficiency desensitizes bone to the effects of mechanical unloading, and that this may be due to an inability of mechanosensing osteocytes to effectively communicate the unloading state to osteoblasts to suppress bone formation. Cx43 may represent a novel therapeutic target for investigation as a countermeasure for age‐related and unloading‐induced bone loss. © 2012 American Society for Bone and Mineral Research.
Clinical, Gross, and Microscopic Findings in Different Avian Species Naturally Infected During the H7N1 Low- and High-Pathogenicity Avian Influenza Epidemics in Italy During 1999 and 2000

Abstract From the end of March to the beginning of December 1999, an epidemic of low-pathogenicity avian influenza (LPAI), caused by a H7N1 type A influenza virus, affected the intensively reared poultry population of Northeastern Italy. A total of 199 flocks were diagnosed with influenza infection. The highest number affected flocks were in meat turkeys (164), with only a limited number of turkey breeder, chicken (breeders, broilers, and table egg layers), and guinea fowl flocks infected. Following the circulation of the LPAI virus in a susceptible population for several months, a high-pathogenicity avian influenza (HPAI) virus emerged. Over 13 million birds on 413 different premises were affected by the HPAI virus, including turkey, chicken, guinea fowl, pheasant, Japanese quail, ostrich, and waterfowl flocks. In the present paper we report on the clinical, gross, histopathological, and immunohistochemical investigations performed on different avian species naturally infected by the LPAI virus and the HPAI virus.
Distinct comparative genomic hybridisation profiles in gastric mucosa‐associated lymphoid tissue lymphomas with and without t(11;18)(q21;q21)

t(11;18)(q21;q21) occurs specifically in mucosa‐associated lymphoid tissue (MALT) lymphoma and the translocation generates a functional API2‐MALT1 fusion product that activates nuclear factor (NF)κB. t(11;18) positive lymphomas usually lack the chromosomal aberrations and microsatellite alterations frequently seen in the translocation‐negative MALT lymphomas. To further understand their genetic differences, we investigated gastric MALT lymphomas with and without t(11;18) by comparative genomic hybridisation. In general, both chromosomal gains and losses were far more frequent in t(11;18)‐negative (median = 3·4 imbalances) than t(11;18)‐positive cases (median = 1·6 imbalances), with gains being more frequent than losses. Recurrent chromosomal gains involving whole or major parts of a chromosome were seen for chromosomes 3, 12, 18 and 22 (23%, 19%, 19% and 27% respectively). Discrete recurrent chromosomal gains were found at 9q34 (11/26 = 42%). Bioinformatic analysis of genes mapping to 9q34 revealed potential targets. Among them, TRAF2 and CARD9 are known interaction partners of BCL10, playing a role in NFκB activation. Interphase fluorescent in situ hybridisation confirmed genomic gain of the TRAF2, CARD9 and MALT1 loci in 5/6 and 2/2 cases showing chromosomal gains at 9q34 and 18q21 respectively. The results further highlight the genetic difference between MALT lymphomas with and without t(11;18). Moreover, our findings suggest that genomic gain of genes that modulate NFκB activation, such as MALT1, TRAF2 and CARD9, may play a role in the pathogenesis of the translocation‐negative MALT lymphoma.
Gene Sequence-Based Criteria for Identification of New Rickettsia Isolates and Description of Rickettsia heilongjiangensis sp. nov

ABSTRACT We propose genetic guidelines for the classification of rickettsial isolates at the genus, group, and species levels by using sequences of the 16S rRNA (rrs) gene and four protein-coding genes, the gltA, ompA, and ompB genes and gene D. To be classified as a member of the genus Rickettsia, an isolate should exhibit degrees of rrs and gltA homology with any of the 20 Rickettsia species studied of ≥98.1 and ≥86.5%, respectively. A member of the typhus group should fulfill at least two of the following four criteria: pairwise nucleotide sequence homologies with rrs, gltA, ompB, and gene D of either Rickettsia typhi or Rickettsia prowazekii of ≥99.4, ≥96.6, ≥92.4, and ≥91.6%, respectively. A member of the spotted fever group should either possess the ompA gene or fulfill at least two of the following four criteria: pairwise nucleotide sequence homologies with rrs, gltA, ompB, and gene D of any member of this group of ≥98.8, ≥92.7, ≥85.8, and ≥82.2%, respectively. The existence of a distinct “ancestral” group should be questioned. To be classified as a new Rickettsia species, an isolate should not exhibit more than one of the following degrees of nucleotide similarity with the most homologous validated species: ≥99.8 and ≥ 99.9% for the rrs and gltA genes, respectively, and, when amplifiable, ≥98.8, ≥99.2, and ≥99.3% for the ompA and ompB genes and gene D, respectively. By use of our classification scheme, “Rickettsia heilongjiangii” belongs to a new species for which we officially propose the name Rickettsia heilongjiangensis sp. nov.
Anatomical study of the iliohypogastric, ilioinguinal, and genitofemoral nerves using high‐resolution ultrasound

Introduction: In this study we aimed to determine whether high‐resolution ultrasound (US) can identify the iliohypogastric (IH), ilioinguinal (II), and genitofemoral (GF) nerves and their relations. Methods: This investigation, initially undertaken in cadavers, was followed by a high‐resolution US study in 30 healthy adult volunteers (180 nerves) by 2 musculoskeletal radiologists on separate occasions, using 2 different approaches (proximal to distal and distal to proximal). A 0–3 scale was used to assess nerve visibility. Location and course of the IH, II, and GF nerves and their relations to adjacent anatomical structures were analyzed. Results: Nerves and their terminal branches were better visualized with the distal‐to‐proximal approach (P < 0.05). Visualization of the terminal branches was possible in up to 60% of volunteers. Conclusions: High‐resolution ultrasound (US) can identify the IH, II, and GF nerves at the level of the abdominal wall and the terminal branches in the majority of volunteers. Muscle Nerve 51: 42–48, 2015
CXCR3 and Its Ligands in a Murine Model of Obliterative Bronchiolitis: Regulation and Function1

Lung transplantation remains the only effective therapy for patients with end-stage lung disease, but survival is limited by the development of obliterative bronchiolitis (OB). The chemokine receptor CXCR3 and two of its ligands, CXCL9 and CXCL10, have been identified as important mediators of OB. However, the relative contribution of CXCL9 and CXCL10 to the development of OB and the mechanism of regulation of these chemokines has not been well defined. In this study, we demonstrate that CXCL9 and CXCL10 are up-regulated in unique patterns following tracheal transplantation in mice. In these experiments, CXCL9 expression peaked 7 days posttransplant, while CXCL10 expression peaked at 1 day and then again 7 days posttransplant. Expression of CXCL10 was also up-regulated in a novel murine model of lung ischemia, and in bronchoalveolar lavage fluid taken from human lungs 24 h after lung transplantation. In further analysis, we found that 3 h after transplantation CXCL10 is donor tissue derived and not dependent on IFN-γ or STAT1, while 24 h after transplantation CXCL10 is from recipient tissue and regulated by IFN-γ and STAT1. Expression of both CXCL9 and CXCL10 7 days posttransplant is regulated by IFN-γ and STAT1. Finally, we demonstrate that deletion of CXCR3 in recipients reduces airway obliteration. However, deletion of either CXCL9 or CXCL10 did not affect airway obliteration. These data show that in this murine model of obliterative bronchiolitis, these chemokines are differentially regulated following transplantation, and that deletion of either chemokine alone does not affect the development of airway obliteration.
Amphetamine‐induced neurochemical and locomotor responses are expressed differentially across the anteroposterior axis of the core and shell subterritories of the nucleus accumbens

The administration of psychostimulants increases dopamine (DA) release within the nucleus accumbens (NAC), a terminal projection site of mesolimbic DA neurons, originating in the ventral tegmental area (VTA). Recent evidence demonstrates that two subdivisions of the NAC, the dorsolateral core and the ventromedial shell, can be distinguished by morphological and immunohistochemical differences, as well as by their distinct anatomical connections. It has been suggested that these two subregions subserve different functions that are related to goal‐directed behaviors, stimulus‐reward associations, and reinforcement induced by addictive drugs. The shell region, in particular, modulates inputs from the limbic system, whereas the core is preferentially innervated by nuclei that process motor information. In the present study, we sought to investigate if (1) the direct infusion of d‐amphetamine (AMPH) by reverse microdialysis into either the core or shell of the NAC across its anteroposterior axis differentially affects dialysate DA and 5‐HT levels, and (2) these subterritories also subserve different behavioral functions. Following the determination of basal DA and 5‐HT levels, four increasing concentrations of AMPH (0.05, 0.10, 0.50, 1.00 μM) were substituted for the dialysis perfusate for 60 min each. Movement units were detected by an infrared sensor and were transmitted through a motion interface to an activity monitor analyzer. AMPH produced a dose‐dependent increase in locomotor activity after microinfusion into either the rostral shell, caudal shell or core of the NAC. The potency of the AMPH‐induced locomotor activating effect was significantly higher in the rostral shell of the NAC compared with the caudal shell and the core. The lowest concentrations of AMPH (0.05, 0.1 μM) produced an equipotent decrease in dialysate DA in either the rostral shell, caudal shell, or core. At 1.0 μM, however, AMPH selectively increased DA in the rostral shell, whereas DA reached baseline values both in the caudal shell and core. Basal dialysate DA levels were significantly higher in the core relative to both the rostral and caudal parts of the shell. The highest dose of AMPH significantly increased dialysate 5‐HT levels over baseline only in the caudal shell of the NAC. The basal dialysate 5‐HT levels did not significantly differ between the three subterritories of the NAC. These results emphasize the heterogeneity and functional compartmentalization within the NAC, the differential regulation of neurochemical and motor responses across the anteroposterior axis of the NAC, and the preferential effect of AMPH in the rostral shell subterritory of the NAC. Synapse 29:310–322, 1998. © 1998 Wiley‐Liss, Inc.
XMAP215 polymerase activity is built by combining multiple tubulin-binding TOG domains and a basic lattice-binding region

XMAP215/Dis1 family proteins positively regulate microtubule growth. Repeats at their N termini, called TOG domains, are important for this function. While TOG domains directly bind tubulin dimers, it is unclear how this interaction translates to polymerase activity. Understanding the functional roles of TOG domains is further complicated by the fact that the number of these domains present in the proteins of different species varies. Here, we take advantage of a recent crystal structure of the third TOG domain from Caenorhabditis elegans, Zyg9, and mutate key residues in each TOG domain of XMAP215 that are predicted to be important for interaction with the tubulin heterodimer. We determined the contributions of the individual TOG domains to microtubule growth. We show that the TOG domains are absolutely required to bind free tubulin and that the domains differentially contribute to XMAP215’s overall affinity for free tubulin. The mutants’ overall affinity for free tubulin correlates well with polymerase activity. Furthermore, we demonstrate that an additional basic region is important for targeting to the microtubule lattice and is critical for XMAP215 to function at physiological concentrations. Using this information, we have engineered a “bonsai” protein, with two TOG domains and a basic region, that has almost full polymerase activity.
Genetic variability in the three genomes of Nasonia: nuclear, mitochondrial and Wolbachia

Nasonia consists of three closely related species of parasitoid wasps that are all infected with the endosymbiotic bacteria Wolbachia, a reproductive parasite common in arthropods. This situation presents the opportunity to compare patterns of variation in three associated genomes, Wolbachia and the nuclear and mitochondrial genomes of its host. Furthermore, although Nasonia wasps are emerging as a model for evolutionary and genetic studies, little is known about their genetic variability. Using amplified fragment length polymorphisms (AFLPs), all three species present a relatively high level of nuclear polymorphism and have different patterns of variation, with one of the species, Nasonia giraulti, being divided into two divergent subgroups. In each species, the mitochondrial pattern of variation is different from the nuclear pattern, possibly due to genetic hitchhiking of the mitochondria during (cytoplasmically inherited) Wolbachia sweeps. Mitochondria in Nasonia show a synonymous substitution rate approximately 10–15‐fold higher than nuclear genes, probably reflecting an elevated mitochondrial mutation rate that is among the highest found in insects. Finally, all three species are doubly infected with their own strains of Wolbachia, one each from the two major supergroups (A and B). Sequence analysis reveals that each of the three Nasonia species acquired their A and B bacteria independently by horizontal transfer events from other insects with the exception of B type Wolbachia in N. longicornis and N. giraulti, which were acquired prior to speciation and then codiverged with the host. This represents one of the few clear‐cut examples of codivergence of Wolbachia during host speciation.
Old and new basal insulin formulations: understanding pharmacodynamics is still relevant in clinical practice

Long‐acting insulin analogues have been developed to mimic the physiology of basal insulin secretion more closely than human insulin formulations (Neutral Protamine Hagedorn, NPH). However, the clinical evidence in favour of analogues is still controversial. Although their major benefit as compared with NPH is a reduction in the hypoglycaemia risk, some cost/effectiveness analyses have not been favourable to analogues, largely because of their higher price. Nevertheless, these new formulations have conquered the insulin market. Human insulin represents currently no more than 20% of market share. Despite (in fact because of) the widespread use of insulin analogues it remains critical to analyse the pharmacodynamics (PD) of basal insulin formulations appropriately to interpret the results of clinical trials correctly. Importantly, these data may help physicians in tailoring insulin therapy to patients' individual needs and, additionally, when clinical evidence is not available, to optimize insulin treatment. For patients at low risk for/from hypoglycaemia, it might be acceptable and also cost‐effective not to use long‐acting insulin analogues as basal insulin replacement. Conversely, in patients with a higher degree of insulin deficiency and increased risk for hypoglycaemia, analogues are the best option due to their more physiological profile, as has been shown in PD and clinical studies. From this perspective optimizing basal insulin treatment, especially in type 2 diabetes patients who are less prone to hypoglycaemia, would be suitable making significant resources available for other relevant aspects of diabetes care.
Physical and Functional Interaction between p53 and the Werner’s Syndrome Protein*

Werner’s syndrome is a human autosomal recessive disorder leading to premature aging. The mutations responsible for this disorder have recently been localized to a gene (WRN) encoding a protein that possesses DNA helicase and exonuclease activities. Patients carrying WRN gene mutations exhibit an elevated rate of cancer, accompanied by increased genomic instability. The latter features are also characteristic of the loss of function of p53, a tumor suppressor that is very frequently inactivated in human cancer. Moreover, changes in the activity of p53 have been implicated in the onset of cellular replicative senescence. We report here that the WRN protein can form a specific physical interaction with p53. This interaction involves the carboxyl-terminal part of WRN and the extreme carboxyl terminus of p53, a region that plays an important role in regulating the functional state of p53. A small fraction of WRN can be found in complex with endogenous p53 in nontransfected cells. Overexpression of WRN leads to augmented p53-dependent transcriptional activity and induction of p21Waf1 protein expression. These findings support the existence of a cross-talk between WRN and p53, which may be important for maintaining genomic integrity and for preventing the accumulation of aberrations that can give rise to premature senescence and cancer.
CHANGE IN THE ACTIVITY OF LECTINS IN CELL STRUCTURE OF WINTER WHEAT CROWN UNDER THE ACTION OF LOW‐TEMPERATURE HARDENING AND FUSICOCCIN

Haemagglutinating activity was determined in cell walls and total cell organelles of crown cells of Winter wheat (Triticum aestivum L.) plants. The effect of fusicoccin (FC) was investigated using fractions obtained from plants hardened for 7 days at 2°C and from untreated plants. FC concentration (5×10−7m) increased the frost resistance of the plants. The temporal pattern of lectin activity during hardening could be described by a single‐peak curve. In the cell wall fraction, the highest activity manifested itself after one‐day hardening, and in the fraction of organelles it peaked after five‐days hardening. The carbohydrate specificity of lectins also changed during hardening; cell wall lectins completely lost their capacity for interaction with uridine diphosphoglucose, glucose 6‐phosphate, D‐galactosamine, and N‐acetylglucosamine and the lectins of organelles retained some affinity only for amino sugars. After hardening the test plants, the activity of the lectins increased substantially in the cell walls and plastids, decreased in the nuclei, and was practically flat in mitochondria and microsomes. Consequently, low temperature and FC with their antistress effect improved frost resistance and stimulated the activity of the lectins of some cell structures of the tillering node of winter wheat. A similar action of low temperature and FC in increasing the activity of lectins of plastids was found. Further information was obtained on the subcellular localization of lectins providing additional information on their possible participation in the development of frost resistance of winter wheat.