Miracle-dz/UniFAR-FTUs huggingface dataset:
EXPRESSION PATTERNS OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN HUMAN CARDIAC ALLOGRAFTS: ASSOCIATION WITH REJECTION

Background. Vascular endothelial growth factor (VEGF), a major angiogenesis factor, has been found to have proinflammatory properties in vivo in several chronic inflammatory diseases. However, little is known of the expression or function of VEGF in acute and chronic allograft rejection. Methods. In a cross‐sectional analysis, we evaluated the expression of VEGF by immunohistochemistry in human endomyocardial biopsies (n=101) from 10 cardiac transplant patients. We correlated expression (scores from 0‐4) with CD3+ T cell, CD68+ monocyte and macrophage infiltrates, or rejection (International Society of Heart and Lung Transplantation grades 0‐4). In addition, we evaluated the temporal patterns of VEGF expression in consecutive biopsies from seven patients (total of 74 biopsies) who were assessed for the development of graft vascular disease (GVD) by intravascular ultrasonography at 1 year posttransplantation. Results. VEGF is expressed in normal human endomyocardial biopsies at low levels and is induced (scores >1) in association with CD3+ T cells (odds ratio [OR], 19.90; P<0.001), CD68+ monocyte and macrophage infiltrates (OR, 8.49; P<0.001), and all grades of acute rejection (OR, 5.4; P<0.001). Increases in VEGF expression were persistent during the first posttransplant year in biopsies from four patients who demonstrated evidence of GVD (mean annual score of 2.3). In contrast, limited expression of VEGF was found in three patients without GVD (mean annual score 1.2). Conclusions. These findings define VEGF as an important proinflammatory cytokine after transplantation and indicate that its expression pattern might identify patients at risk for the development of GVD.
Effect of NG-nitro-L-arginine methyl ester and L-arginine on ethanol-induced gastric mucosal damage in newborn rats

Previous studies have suggested that the mechanisms involved in gastric mucosal protection in newborn rats are different from those in adult rats. The aim of this study was to determine whether nitric oxide (NO) has protective effects against ethanol-induced gastric mucosal damage in newborn rats. In 1-week-old rats, (1) pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, increased gastric mucosal damage induced by 35% ethanol dose-dependently (0.3-30 mg/kg), (2) concurrent administration of 300 mg/kg L-arginine (L-Arg) inhibited the L-NAME induced-increase in damage completely, and (3) pretreatment with low dose L-Arg (30 mg/kg) decreased the mucosal damage induced by 60% ethanol. We concluded that endogeneous NO is involved in the protective mechanism of the gastric mucosa in neonatal rats.
Central proopiomelanocortin but not neuropeptide Y mediates sympathoexcitation and hypertension in fat fed conscious rabbits

Objective: High-fat diet (HFD)-induced hypertension in rabbits is neurogenic because of the central sympathoexcitatory actions of leptin. Hypothalamic melanocortin and neuropeptide Y (NPY) neurons are recognized as the major signalling pathways through which leptin exerts its central effects. In this study, we assessed the effects of specific antagonists and agonists to melanocortin and NPY receptors on HFD-induced sympathoexcitation and hypertension. Methods: Rabbits were instrumented with intracerebroventricular cannula, renal sympathetic nerve activity (RSNA) electrode, and blood pressure telemetry transmitter. Results: After 3 weeks HFD (13.5% fat, n = 12) conscious rabbits had higher RSNA (+3.8 nu, P = 0.02), blood pressure (+8.6 mmHg, P < 0.001) and heart rate (+15 b/min, P = 0.01), and brain-derived neurotrophic factor levels in the hypothalamus compared with rabbits fed a control diet (4.2% fat, n = 11). Intracerebroventricular administration of the melanocortin receptor antagonist SHU9119 reduced RSNA (−2.7 nu) and blood pressure (−8.5 mmHg) in HFD but not control rabbits, thus reversing 100% of the hypertension and 70% of the sympathoexcitation induced by a HFD. By contrast, blocking central NPY Y1 receptors with BVD10 increased RSNA only in HFD rabbits. Intracerebroventricular &agr;-melanocortin stimulating hormone increased RSNA and heart rate (P < 0.001) in HFD rabbits but had no effect in control rabbits. Conclusion: These findings suggest that obesity-induced hypertension and increased RSNA are dependent on the balance between greater activation of melanocortin signalling through melanocortin receptors and lesser activation of NPY sympathoinhibitory signalling. The amplification of the sympathoexcitatory effects of &agr;-melanocortin stimulating hormone also indicates that the underlying mechanism is related to facilitation of leptin–melanocortin signalling, possibly involving chronic activation of brain-derived neurotrophic factor.
Cardioactive properties of Solanaceae plant extracts and pure glycoalkaloids on Zophobas atratus

Glycoalkaloids, the biologically active secondary metabolites produced by Solanaceae plants, are natural defenses against animals, insects and fungi. In this paper, the effects of glycoalkaloids present in extracts of Solanaceae plants (potato, tomato and black nightshade) or pure commercial glycoalkaloids on the coleopteran Zophobas atratus F. were evaluated by in vitro and in vivo bioassays using heart experimental models. Each tested extract induced a dose‐dependent cardioinhibitory effect. The perfusion of Zophobas atratus semi‐isolated heart using the highest potato and tomato extract concentration (1 mmol/L) caused irreversible cardiac arrests, while extract from black nightshade produced fast but reversible arrests. Pure commercial glycoalkaloids caused similar but less evident effects compared with extracts. Our results showed that the bioactivity of tested compounds depended on their structure and suggested the existence of synergistic interactions when combinations of the main glycoalkaloids of potato and black nightshade were used for trials. Surprisingly, injection of tomato and potato extracts in 1‐day‐old pupae of Zophobas atratus induced reversible positive chronotropic effects and decreased the duration of the both phases (anterograde and retrograde) of the heart contractile activity. Furthermore, these extracts affected the amplitude of the heart contractions.
Reduction of Unusual Iron-Sulfur Clusters in the H2-sensing Regulatory Ni-Fe Hydrogenase from Ralstonia eutropha H16*

The regulatory Ni-Fe hydrogenase (RH) from Ralstonia eutropha functions as a hydrogen sensor. The RH consists of the large subunit HoxC housing the Ni-Fe active site and the small subunit HoxB containing Fe-S clusters. The heterolytic cleavage of H2 at the Ni-Fe active site leads to the EPR-detectable Ni-C state of the protein. For the first time, the simultaneous but EPR-invisible reduction of Fe-S clusters during Ni-C state formation was demonstrated by changes in the UV-visible absorption spectrum as well as by shifts of the iron K-edge from x-ray absorption spectroscopy in the wild-type double dimeric RHWT [HoxBC]2 and in a monodimeric derivative designated RHstop lacking the C-terminal 55 amino acids of HoxB. According to the analysis of iron EXAFS spectra, the Fe-S clusters of HoxB pronouncedly differ from the three Fe-S clusters in the small subunits of crystallized standard Ni-Fe hydrogenases. Each HoxBC unit of RHWT seems to harbor two [2Fe-2S] clusters in addition to a 4Fe species, which may be a [4Fe-3S-3O] cluster. The additional 4Fe-cluster was absent in RHstop. Reduction of Fe-S clusters in the hydrogen sensor RH may be a first step in the signal transduction chain, which involves complex formation between [HoxBC]2 and tetrameric HoxJ protein, leading to the expression of the energy converting Ni-Fe hydrogenases in R. eutropha.
Predictors of Hemorrhage Following Intra-Arterial Thrombolysis for Acute Ischemic Stroke: The Role of Pial Collateral Formation

BACKGROUND AND PURPOSE: The extent of pial collateral formation during acute ischemic stroke has been shown to influence outcomes. This study examines whether angiographic assessment of pial collateral formation is predictive of hemorrhagic transformation following intra-arterial thrombolysis (IAT) for acute ischemic stroke. MATERIALS AND METHODS: Rates of any hemorrhage and significant hemorrhage (>25 mL) were reviewed in 104 consecutive patients who underwent IAT following acute ischemic stroke. The influence of the anatomic extent of pial collateral formation on the rates of hemorrhage and significant hemorrhage relative to known predictors for hemorrhagic transformation (presenting systolic blood pressure, blood glucose level, platelet level, and National Institutes of Health Stroke Scale [NIHSS] score, history of diabetes, time to treatment, age, sex, occlusion site, and extent of reperfusion) was analyzed by using logistic regression models. RESULTS: Rates of any hemorrhage and significant hemorrhage were 25.2% (26/104) and 9.7% (10/104), respectively. The rate of significant hemorrhage was 25.0% (8/32) in patients with poor pial collaterals and 2.78% (2/72) in those with good pial collaterals (P = .0004, Pearson correlation). The rate of any hemorrhage was also significantly higher in patients with poor pial collaterals (40.6% versus 18.1%; P = .0142, Pearson correlation). Logistic regression analyses revealed that pial collateral formation (odds ratio [OR] = 3.04), history of diabetes (OR = 4.83), platelets <200,000/μL (OR = 2.95), and time to treatment <3 hours (OR = 12.0) were statistically significant predictors of hemorrhage, whereas pial collateral formation (OR = 13.1) and platelets <200,000/μL (OR = 8.1) were statistically significant predictors of significant hemorrhage. CONCLUSIONS: Poor pial collateral formation is associated with higher incidence and larger size of hemorrhage following IAT.
LILRB3 (ILT5) is a myeloid checkpoint on myeloid cells that elicits profound immununomodulation

Despite advances in identifying the key immunoregulatory roles of many of the human leukocyte immunoglobulin (Ig)-like receptor (LILR) family members, the function of the inhibitory molecule LILRB3 (ILT5, CD85a, LIR3) remains unclear. Studies indicate a predominant myeloid expression; however, high homology within the LILR family and a relative paucity of reagents have hindered progress for this receptor. To investigate its function and potential immunomodulatory capacity, a panel of LILRB3-specific monoclonal antibodies (mAb) was generated. LILBR3-specific mAb bound to discrete epitopes in either Ig-like domain two or four. LILRB3 ligation on primary human monocytes by agonistic mAb resulted in phenotypic and functional changes, leading to potent inhibition of immune responses in vitro, including significant reduction in T cell proliferation. Importantly, agonizing LILRB3 in humanized mice induced tolerance and permitted efficient engraftment of allogeneic cells. Our findings reveal powerful immunosuppresive functions of LILRB3 and identify it as an important myeloid checkpoint receptor.
Association of Mycobacterium avium subspecies paratuberculosis With Crohn Disease in Pediatric Patients

Objectives: The aim of the present study was to determine the prevalence of Mycobacterium avium subsp paratuberculosis (MAP) DNA in intestinal biopsies from pediatric patients with granulomatous Crohn disease (CD) or ulcerative colitis (UC), and matched control subjects without inflammatory bowel disease (IBD). Patients and Methods: DNA was extracted from formalin-fixed paraffin-embedded colonic and ileal biopsies from patients with CD (n = 22) or UC (n = 20), and from controls without IBD (n = 21). IS900 nested polymerase chain reaction was performed in triplicate to determine the presence of MAP-specific DNA. Results: In mucosal biopsies from terminal ileum, IS900 amplicons were detected in 1 of 19 (5.2%) control subjects, 1 of 20 (5%) patients with UC, and 7 of 20 (35%) patients with CD (P < 0.05 vs controls, odds ratio 9.6). In colonic biopsies, IS900 amplicons were detected in 0 of 19 control subjects, 1 of 19 (5.2%) patients with UC, and 5 of 19 (26.3%) patients with CD (P < 0.05 vs controls, odds ratio 14.8). In patients with CD, there was no correlation between disease activity and the presence of IS900. Conclusions: Our technique enabled sensitive and specific detection of MAP DNA in archival endoscopic biopsy specimens. Although MAP-specific DNA can be detected in about 5% of intestinal biopsies from children with UC or controls without IBD, its presence was significantly associated with pediatric granulomatous CD, being particularly prevalent in ileal tissue. This easily defined clinical subset of patients may be useful for additional studies to determine the role of MAP in CD.
Extensive transfer of genes for edible seaweed digestion from marine to human gut bacteria

Humans harbor numerous species of colonic bacteria that digest the fiber polysaccharides in commonly consumed terrestrial plants. More recently in history, regional populations have consumed edible macroalgae seaweeds containing unique polysaccharides. It remains unclear how extensively gut bacteria have adapted to digest these nutrients and use these abilities to colonize microbiomes around the world, especially outside Asia. Here, we show that the ability of gut bacteria to digest seaweed polysaccharides is more pervasive than previously appreciated. Using culture-based approaches, we show that known Bacteroides genes involved in seaweed degradation have mobilized into many members of this genus. We also identify several previously unknown examples of marine bacteria-derived genes, and their corresponding mobile DNA elements, that are involved in degrading seaweed polysaccharides. Some of these genes reside in gut-resident, Gram-positive Firmicutes, for which phylogenetic analysis suggests an origin in the Epulopiscium gut symbionts of marine fishes. Our results are important for understanding the metabolic plasticity of the human gut microbiome, the global exchange of genes in the context of dietary selective pressures and identifying new functions that can be introduced or engineered to design and fill orthogonal niches for a future generation of engineered probiotics.
Sense of Belonging as a Predictor of Reasons for Living in Older Adults

In response to the high rate of suicide among aging people, this study investigated sense of belonging as a predictor of reasons for living in an aged sample. A community sample of 104 Australians aged 61 to 95 years completed The Reasons for Living Inventory and The Sense of Belonging Instrument. Results indicated that a higher sense of belonging predicted more reasons to live overall, and child-related concerns, responsibility to family, and survival and coping beliefs, specifically. Future research should investigate if the enhancement of a sense of belonging among older adults is associated with an increase in reasons for living.
Tumor proliferation, p53 expression, and apoptosis in laryngeal carcinoma

Radiotherapy is used in the treatment of laryngeal carcinoma. The search for biologic parameters that could be used to identify patients who will respond to radiotherapy is crucial. The aim of this study was to determine whether the Ki‐67 and p53 indices and the pretreatment apoptotic index would be useful in predicting local control and survival for a group of laryngeal carcinoma patients given postoperative radiotherapy.
Transcranial Magnetic Stimulation and Epilepsy

Summary Transcranial magnetic stimulation has been used to study generalized and focal epilepsies for more than a decade. The technique appears safe and has yielded important information about the mechanisms underlying epilepsy. Transcranial magnetic stimulation findings differ depending on the epilepsy syndrome, lending support to the concept that there are distinct pathophysiologies underlying each condition. In most studies of generalized epilepsies, transcranial magnetic stimulation has indicated a state of relative hyperexcitability of excitatory cortical interneurons and possibly inhibitory interneurons as well, which can be reversed through the actions of anticonvulsant medications. Transcranial magnetic stimulation studies in patients with a seizure focus in the motor cortex indicate increased cortical excitability and reduced inhibition, but in patients with seizure foci located elsewhere the findings are similar to those in generalized epilepsies. Transcranial magnetic stimulation has also been used to study the mode of action of anticonvulsants and may prove to be a useful means of testing the potential for new drugs to act as anticonvulsants. Repetitive transcranial magnetic stimulation may prove to have a therapeutic role by producing long-lasting cortical inhibition after a train of impulses.
Genetic and environmental controls of microbial communities on leaf litter in streams

Summary 1. Despite the importance of microorganisms for leaf litter decomposition in streams, little is known about which factors affect community composition of bacterial and fungal communities. Standard morphological techniques probably underestimate microbial diversity. 2. We used terminal restriction fragment length polymorphisms of the ITS regions for fungi, and the 16S region for bacteria, to compare fungal and bacterial communities on four cross types of cottonwood leaves (Populus fremontii, P. angustifolia, and their naturally occurring F1 and backcross hybrids). Decomposing leaves were studied in two Arizona rivers that differ in water chemistry and macroinvertebrates. 3. Hybridising cottonwoods are an ideal model system to test how genetic differences in leaf litter chemistry affect microbial communities because cross types have different decomposition rates and leaf litter chemistry. Leaves were incubated in litter bags for 2 weeks and brought to the laboratory for genetic analysis. Communities were analysed using non-metric multi dimensional scaling (NMDS) and diversity indices. 4. Fungal and bacterial communities differed between the two rivers, even when growing on identical substrates. There were also significant differences in microbial communities among the four cross types, indicating that genetically based differences in leaf litter translate to differences in microbial communities. 5. Diversity increased along the hybridising complex from P. fremontii to P. angustifolia, with hybrids showing intermediate values. Fungal and bacterial diversity were significantly higher on cross types with higher tannin concentrations and slower decomposition rates. 6. Environmental conditions most strongly structured microbial communities, but within an environment, genetic-based differences in leaf litter quality yielded differences in diversity and community structure. 7. Molecular tools are making it possible to understand patterns of microbial diversity in river ecosystems, paving the way for a better understanding of how differences in microbial species affect ecosystem processes and higher trophic levels.
Combined Ultrasonic Thermal Ablation with Interleaved ARFI Image Monitoring Using a Single Diagnostic Curvilinear Array: A Feasibility Study

The goal of this work is to demonstrate the feasibility of using a diagnostic ultrasound system (Siemens Antares™ and CH6–2 curvilinear array) to ablate ex vivo liver with a custom M-mode sequence and monitor the resulting tissue stiffening with 2-D Acoustic Radiation Force Impulse (ARFI) imaging. Images were taken before and after ablation, as well as in 5- s intervals during the ablation sequence in order to monitor the ablation lesion formation temporally. Ablation lesions were generated at depths up to 1.5 cm from the surface of the liver and were not visible in B-mode. ARFI images showed liver stiffening with heating that corresponded to discolored regions in gross pathology. As expected, the contrast of ablation lesions in ARFI images is observed to increase with ablation lesion size. This study demonstrated the ability of a diagnostic system using custom beam sequences to localize an ablation site, heat the site to the point of irreversible damage and monitor the formation of the ablation lesion with ARFI imaging.
Modern corporate changes: reinstating the link between the nature, boundaries and governance of the firm

The theory of the firm and corporate governance are two fields of analysis traditionally tackled separately in the economic literature. This paper seeks to rediscover the link between the nature, boundaries and governance of the firm on the basis of changes in corporate industrial firms. We advance the argument that, to understand the human capital‐intensive firm, this analytical interconnection should be restored. On the basis of critical resource theory, we present an innovative vision of the nature, boundaries and governance of firms whose productive activity is built around its key partners’ human capital. The organisational mode of governance has changed, linked to a renewed conception of the firm. What we term the ‘multi‐resources’ model of governance of the firm depends on an original representation of the structure, organisation and power relationships of modern firms, whose value arises from the accumulation of specific human capital. Consequently, the multi‐resources model involves hybrid governance instrument in order to protect the integrity of the human capital‐intensive firm.
Effects of the human intestinal flora on germ-free mice.

The effects of complete human intestinal flora and of intestinal anaerobes on germ-free mice were studied. The gross composition of the flora of mice was similar to that of the flora with which the animals had been contaminated and appeared to be stable provided that the animals were kept isolated. The complete flora and the anaerobes reduced caecal weight to normal values and induced an antagonistic effect against Escherichia coli. In contrast to the complete flora, the anaerobes were not invasive in immunosuppressed mice and induced colonization resistance and antagonism against Pseudomonas aeruginosa.
Structural and energetic basis of ALS-causing mutations in the atypical proline–tyrosine nuclear localization signal of the Fused in Sarcoma protein (FUS)

Mutations in the proline/tyrosine–nuclear localization signal (PY-NLS) of the Fused in Sarcoma protein (FUS) cause amyotrophic lateral sclerosis (ALS). Here we report the crystal structure of the FUS PY-NLS bound to its nuclear import receptor Karyopherinβ2 (Kapβ2; also known as Transportin). The FUS PY-NLS occupies the structurally invariant C-terminal arch of Kapβ2, tracing a path similar to that of other characterized PY-NLSs. Unlike other PY-NLSs, which generally bind Kapβ2 in fully extended conformations, the FUS peptide is atypical as its central portion forms a 2.5-turn α-helix. The Kapβ2-binding epitopes of the FUS PY-NLS consist of an N-terminal PGKM hydrophobic motif, a central arginine-rich α-helix, and a C-terminal PY motif. ALS mutations are found almost exclusively within these epitopes. Each ALS mutation site makes multiple contacts with Kapβ2 and mutations of these residues decrease binding affinities for Kapβ2 (KD for wild-type FUS PY-NLS is 9.5 nM) up to ninefold. Thermodynamic analyses of ALS mutations in the FUS PY-NLS show that the weakening of FUS-Kapβ2 binding affinity, the degree of cytoplasmic mislocalization, and ALS disease severity are correlated.