Miracle-dz/UniFAR-FTUs huggingface dataset:
Tissue- and Cell-Specific Co-localization of Intracellular Gelatinolytic Activity and Matrix Metalloproteinase 2

Matrix metalloproteinase 2 (MMP-2) is a proteolytic enzyme that degrades extracellular matrix proteins. Recent studies indicate that MMP-2 also has a role in intracellular proteolysis during various pathological conditions, such as ischemic injuries in heart and brain and in tumor growth. The present study was performed to map the distribution of intracellular MMP-2 activity in various mouse tissues and cells under physiological conditions. Samples from normal brain, heart, lung, liver, spleen, pancreas, kidney, adrenal gland, thyroid gland, gonads, oral mucosa, salivary glands, esophagus, intestines, and skin were subjected to high-resolution in situ gelatin zymography and immunohistochemical staining. In hepatocytes, cardiac myocytes, kidney tubuli cells, epithelial cells in the oral mucosa as well as in excretory ducts of salivary glands, and adrenal cortical cells, we found strong intracellular gelatinolytic activity that was significantly reduced by the metalloprotease inhibitor EDTA but not by the cysteine protease inhibitor E-64. Furthermore, the gelatinolytic activity was co-localized with MMP-2. Western blotting and electron microscopy combined with immunogold labeling revealed the presence of MMP-2 in different intracellular compartments of isolated hepatocytes. Our results indicate that MMP-2 takes part in intracellular proteolysis in specific tissues and cells during physiological conditions.
Developments towards formalizing a benchmark for continuous-time model identification

The identification of continuous-time models of dynamical systems based on sampled measurements of input and output signals is a research topic that has received much attention during the past decades. However, a framework for the correct assessment of the performance of various estimation methods, as well as their numerical reliability, is still missing due to a number of benchmarking difficulties, equally applicable to both discrete- and continuous-time identification problems. This paper revisits this topic, reports new numerical results, highlights several fundamental aspects regarding the definition of an appropriate benchmark for the evaluation of continuous-time linear model identification algorithms and discusses several means of addressing the related existing problems.
Early pregnancy Estrogen-dependent regulation of human uterine natural killer cells promotes vascular remodelling via secretion of CCL 2

D.A. Gibson1, E. Greaves2, H.O. D. Critchley2, and P.T. K. Saunders1,* Medical Research Council Centre for Inflammation Research, The University of Edinburgh, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
Suicide Prevention: College Students' Intention to Intervene

The objective of this article was to examine college students' intention to intervene with a suicidal individual and examine the Willingness to Intervene against Suicide questionnaire (WIS). College students (n = 1065) completed an online questionnaire about their attitudes, subjective norms, and perceived behavioral control regarding suicide and suicide intervention as well as their intention to intervene with a suicidal individual. The data were analyzed using confirmatory factor analysis, reliability analysis, and multiple regression. It was found that the WIS significantly predicted intention to intervene with a suicidal individual. The WIS was internally consistent with adequate goodness-of-fit indices for three of the four sub-scales. The WIS is an effective tool for predicting intention to intervene; however, the subjective norms sub-scale should be revised to improve the model.
Photolabeling Identifies a Putative Fusion Domain in the Envelope Glycoprotein of Rabies and Vesicular Stomatitis Viruses (*)

Vesicular stomatitis and rabies viruses enter cells through receptor-mediated endocytosis, followed by fusion of the viral with the endosomal membrane. The latter step is catalyzed by the viral envelope glycoprotein, which, in the low pH environment of the endosome, undergoes a conformational transition to a fusion-competent state. To investigate whether fusion competence involves the low pH exposure of a hydrophobic fusion region(s), we have applied hydrophobic photolabeling using the recently developed phospholipid analogue 1-O-hexadecanoyl-2-O-[9-[[[2-[I]iodo-4-(trifluoromethyl-3H-diazirin-3-yl)benzyl]oxy]carbonyl] nonanoyl]-sn-glycero-3-phosphocholine ([I]TID-PC/16) (Weber, T., and Brunner, J.(1995) J. Am. Chem. Soc. 117, 3084-3095). Rosettes of rabies virus glycoprotein, whole rabies virus, or vesicular stomatitis virus were incubated with large unilamellar vesicles containing [I]TID-PC/16. Following reagent activation, the labeled glycoprotein was isolated and analyzed. In all cases, labeling of the glycoprotein strongly increased as the pH was lowered from 7.0 to 6.0, suggesting the exposure at acidic pH of a domain capable of interacting with membranes. To identify the labeled region(s), CNBr fragments were generated and analyzed by SDS-polyacrylamide followed by autoradiography. In rabies glycoprotein, the labeled segment was found to be contained within fragment RCr5 (residues 103-179). Glycoprotein from vesicular stomatitis virus was labeled within fragment VCr1 (residues 59-221). These results demonstrate that rhabdovirus glycoprotein contains a domain that at low pH is capable of interacting with a target membrane in a hydrophobic manner. This domain may play a role similar to that of the fusion peptide found in many other viral fusion proteins.
Viande de lapin et oméga 3 Une alimentation riche en luzerne permet d'enrichir la viande des lapins en oméga 3

Selon les Apports Nutritionnels Recommandes pour la population francaise, l'alimentation humaine devrait apporter des matieres grasses dont le rapport entre l'acide linoleique et l'acide α-linolenique soit egal a 5. En realite dans notre alimentation, il est de l'ordre de 20. Le profil en acide gras de la viande de lapin depend principalement de celui des acides gras ingeres. La luzerne deshydratee, matiere premiere classiquement introduite dans les rations, est riche en acide α-linolenique. Son utilisation en production cunicole permet ainsi la production d'une viande satisfaisant aux besoins nutritionnels de l'homme.
Anatomia Humana, Uma Disciplina que Causa Evasão e Exclusão: Quando a Hipótese Principal Não se Confirma

RESUMO Esta pesquisa e do tipo descritiva exploratoria e tem por objetivo investigar possiveis causas de evasao e exclusao na disciplina de Anatomia Humana dos cursos de Educacao Fisica (Licenciatura e Bacharelado), no Centro Universitario Metodista do IPA. A pesquisa levanta questoes e implicacoes com relacao ao metodo de ensino do professor da disciplina e compara o metodo classico de ensinar a Anatomia Humana com metodos mais atuais e inovadores. A disciplina de Anatomia Humana e de carater basico e imprescindivel para a formacao de um futuro Educador Fisico. Os dados foram coletados com dois questionarios aplicados a uma turma de 32 alunos dos cursos de Educacao Fisica matriculados na disciplina de Anatomia Humana em 2011. Pela nao confirmacao da hipotese principal foi necessario posteriormente coletar outros dados por meio de duas entre vistas. Pode-se constatar que um metodo diferenciado de ensinar a Anatomia Humana evita que os alunos se sintam excluidos ou abandonem a disciplina.
Ultrastructural Localization of Iron in the Human Jejunum in Iron Overload (Bantu Siderosis)

Summary. Light and electron microscopical studies of intestinal biopsies from 22 patients with advanced Bantu siderosis revealed that ferritin‐iron was deposited in dense membrane‐bound ferritin bodies, in apical vesicles and in Golgi vesicles of the jejunal absorptive cells. Acid phosphatase was demonstrated within the ferritin bodies and it was concluded that these bodies were lysosomes. Ferritin molecules were also observed in the intercellular space between epithelial cells and cells of the lamina propria, and within the lumen of capillaries.
Antiplatelet Therapy after Percutaneous Coronary Intervention

There is intense interest in the relationship between inflammation, thrombosis, platelet aggregation, and hyperlipidemia in patients with coronary artery disease. The specific role of inflammation with its linkage to the coagulation cascade has been well studied. A number of inflammatory markers have been identified which can be used for risk stratification in patients with acute coronary syndromes. Patients with acute coronary syndromes at the time of presentation often have an underlying inflammatory state which needs therapy with antiplatelet regimens including now increasingly frequently clopidogrel in addition to the standard of aspirin. In those patients who are treated medically for their acute coronary syndromes, long-term treatment with dual antiplatelet therapy has been documented to be associated with improved outcome. In patients who undergo an invasive approach with placement of intracoronary stents, the importance of dual antiplatelet therapy is increased. Drug-eluting stents are now used in approximately 90% of all interventional procedures. There is evidence to suggest that while these patients have improved outcome in terms of a decreased need for subsequent procedures to treat restenosis, there is the potential for late subacute stent thrombosis. When late subacute stent thrombosis occurs, it results in mortality or infarction in 40–60% of patients. Dual antiplatelet therapy is therefore recommended for an increasingly longer time in this patient group. At the present time, protocols indicate 3 months for one of the drug-eluting stents and 6 months for the other. However, increasingly longer antiplatelet therapy is being used clinically. Assessment of platelet function during follow-up is as yet early. There are issues about which specific test to use and the definition of platelet hyperreactivity. In the future, more individually targeted therapy may be possible if we can more adequately assess the degree of hyperreactivity and underlying inflammation.
Child Sexual Abuse and Mandatory Reporting Intervention Preservice Content Preferred by Student Teachers

The importance of preservice university teacher training about child sexual abuse and its mandatory reporting intervention is addressed in educational literature, although very little is known about student teachers’ learning interests and preferences in this area. In this article, student teachers refer to students in university who are training to become teachers whose training includes teaching experiences in schools. This study examines the content about child sexual abuse and its intervention that student teachers believe they should learn. Results based on quantitative analyses show the relative importance of gender in determining responses to questions about university training and, to a lesser extent, the importance of a previous acquaintance with victims of sexual abuse, previous employment, and the length of the university course. Results based on qualitative data show that content knowledge preferred by elementary/primary and secondary school student teachers includes the teacher's role in mandatory reporting of child sexual abuse and signs, experiences, and responses to student disclosure. Student teachers prefer content examples of school professionals’ responses and procedures after disclosure and prefer direct learning content from intervening school professionals. These outcomes could usefully guide teachers and educators who design intervention curricula on child sexual abuse for preservice teachers.
Loss of Ikkβ Promotes Migration and Proliferation of Mouse Embryo Fibroblast Cells*

The IκB kinase complex (IKK) is central to the activation of NF-κB, a critical transcription factor governing expression of genes involved in cell proliferation and anti-apoptotic responses. Mice with genetic disruptions of the Ikkβ or Ikkγ gene loci die during embryogenesis because of severe hepatic apoptosis. We now show that Ikkβ gene deficiency promotes migration and proliferation of mouse embryo fibroblast cells. Morphological analyses revealed an unusual protrusion of the cytoplasm in Ikkβ-/- cells when cultured at a lower density. In a Boyden chamber assay, Ikkβ-/- cells exhibited a high rate of invasion and migration. Enhanced formation of actin stress fibers was also observed in the Ikkβ-/- cells. Mechanistic studies indicated that IKKβ affects the expression of proteins involved in the assembly of cytoskeleton and cell movement. Furthermore, re-expression of Ikkβ and antioxidant treatment in Ikkβ-/- cells caused a reversal of protrusive phenotype and high motility, respectively. Furthermore, elimination of reactive oxygen species (ROS) blocked expression of snail and subsequently derepressed E-cadherin expression. Although the underlying mechanism is likely entangled and complicated, the data presented indicate that generation of ROS played a key role in the morphological and mobility changes in Ikkβ-/- cells. These data thus suggest that IKKβ provides inhibitory signals for cell mobility and growth. Deficiency in the Ikkβ gene promotes cell mobilization, at least partially, through a ROS-dependent mechanism.
Heterogeneous requirement of IkappaB kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis: implications for therapy.

OBJECTIVE To investigate the potential role of IkappaB kinase 1 (IKK-1) and IKK-2 in the regulation of nuclear factor kappaB (NF-kappaB) activation and the expression of tumor necrosis factor alpha (TNFalpha), as well as interleukin-1beta (IL-1beta), IL-6, IL-8, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs), in rheumatoid arthritis (RA). METHODS Recombinant adenoviruses expressing beta-galactosidase, dominant-negative IKK-1 and IKK-2, or IkappaBalpha were used to infect ex vivo RA synovial membrane cultures and synovial fibroblasts obtained from patients with RA undergoing joint replacement surgery, or human dermal fibroblasts, human umbilical vein endothelial cells (HUVECs), and monocyte-derived macrophages from healthy volunteers. Then, their effect on the spontaneous or stimulus-induced release of inflammatory cytokines, VEGF, and MMPs from RA synovial membrane cells was examined. RESULTS IKK-2 was not required for lipopolysaccharide (LPS)-induced NF-kappaB activation or TNFalpha, IL-6, or IL-8 production in macrophages, but was essential for this process in response to CD40 ligand, TNFalpha, and IL-1. In synovial fibroblasts, dermal fibroblasts, and HUVECs, IKK-2 was also required for LPS-induced NF-kappaB activation and IL-6 or IL-8 production. In RA synovial membrane cells, IKK-2 inhibition had no effect on spontaneous TNFalpha production but significantly reduced IL-1beta, IL-6, IL-8, VEGF, and MMPs 1, 2, 3, and 13. CONCLUSION Our study demonstrates that IKK-2 is not essential for TNFalpha production in RA. However, because IKK-2 regulates the expression of other inflammatory cytokines (IL-1beta, IL-6, and IL-8), VEGF, and MMPs 1, 2, 3, and 13, which are involved in the inflammatory, angiogenic, and destructive processes in the RA joint, it may still be a good therapeutic target.
Short-term effects of timber harvest and forest edges on ground-layer mosses and liverworts

Limited information exists on the effects of forest management practices on bryophytes, despite their impor- tance to forest ecosystems. We examined short-term responses of ground-layer bryophytes to logging disturbance and creation of edges in mature Pseudotsuga forests of western Washington (USA). The abundance and richness of species were measured in four 1-ha forest aggregates (patches of intact forest) and in surrounding logged areas before and after structural retention harvests. One year after treatment, species richness, total cover, and frequency of most moss and liverwort taxa declined within harvest areas. Within forest aggregates, mosses did not show significant edge effects; however, richness and abundance of liverworts declined with proximity to the aggregate edge. Our results suggest that, over short time frames, 1-ha-sized aggregates are sufficient to maintain most common mosses through structural reten- tion harvests but are not large enough to prevent declines or losses of liverworts. Thus, current standards for structural retention, which allow for aggregates as small as 0.2 ha, may be inadequate to retain the diversity and abundance of species found in mature, undisturbed forests.
Prolyl-hydroxylase inhibitor activating hypoxia-inducible transcription factors reduce levels of transplant arteriosclerosis in a murine aortic allograft model.

OBJECTIVES The development of transplant arteriosclerosis, the hallmark feature of heart transplant rejection, is associated with a chronic immune response and also influenced by an initial injury to the graft through ischaemia and reperfusion. Hypoxia-inducible transcription factor (HIF)-1 pathway signalling has a protective effect against ischaemia-reperfusion injury and has already been demonstrated to ameliorate allograft nephropathy in previous animal studies. Therefore, the aim of this study was to investigate the effect of stabilization of hypoxia-inducible transcription factors with a prolyl-hydroxylase domain (PHD) inhibitor on transplant arteriosclerosis in an experimental aortic allograft model. METHODS MHC-class I mismatched C.B10-H2(b)/LilMcdJ donor thoracic aortas were heterotopically transplanted into the abdominal aorta of BALB/c mice. Donor animals received a single dose of the PHD inhibitor 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate (ICA) (40 mg/kg) or vehicle i.p. 4 h before transplantation. Intragraft HIF accumulation after ICA treatment was detected by immunohistochemistry before and after cold ischaemia (n = 5). Grafts were harvested 30 days after transplantation and analysed by histology (n = 7) and immunofluorescence (n = 7). In addition, intragraft mRNA expression for cytokines, adhesion molecules and growth factors was determined on Day 14 (n = 7). RESULTS Donor preconditioning with ICA resulted in HIF accumulation in the aorta and induction of the HIF target genes vascular endothelial growth factor and transforming growth factor-beta. Vascular lesions were present in both experimental groups. However, there was significantly reduced intimal proliferation in preconditioned grafts when compared with vehicle controls [intimal proliferation 31.3 ± 8% (ICA) vs 55.3 ± 20% (control), P < 0.01]. In addition, experimental groups revealed a down-regulation of E-selectin (-57%) and MCP1 (-33%) expression after ICA pretreatment compared with controls, going along with decreased T-cell [1.4% CD4+ T-cell infiltration vs 8.4% (control) and 4.9% CD8+ T-cell infiltration vs 10.7% (control)], dendritic cell (0.6% dendritic cells infiltration vs 1.9% infiltration(control)] and macrophage infiltration [4.8% macrophages (ICA) vs 10.9% (control)] within vascular grafts. CONCLUSIONS These data of an animal transplant model show that the pharmaceutical activation of HIF with endogenous up-regulation of protective target genes leads to adaptation of the graft to low oxygen-saturation and hereby attenuates the development of transplant arteriosclerosis and allograft injury. Pharmaceutical inhibition of PHDs appears to be a very attractive strategy for organ preservation that deserves further clinical evaluation.
VDAC2 Inhibits BAK Activation and Mitochondrial Apoptosis

The multidomain proapoptotic molecules BAK or BAX are required to initiate the mitochondrial pathway of apoptosis. How cells maintain the potentially lethal proapoptotic effector BAK in a monomeric inactive conformation at mitochondria is unknown. In viable cells, we found BAK complexed with mitochondrial outer-membrane protein VDAC2, a VDAC isoform present in low abundance that interacts specifically with the inactive conformer of BAK. Cells deficient in VDAC2, but not cells lacking the more abundant VDAC1, exhibited enhanced BAK oligomerization and were more susceptible to apoptotic death. Conversely, overexpression of VDAC2 selectively prevented BAK activation and inhibited the mitochondrial apoptotic pathway. Death signals activate “BH3-only” molecules such as tBID, BIM, or BAD, which displace VDAC2 from BAK, enabling homo-oligomerization of BAK and apoptosis. Thus, VDAC2, an isoform restricted to mammals, regulates the activity of BAK and provides a connection between mitochondrial physiology and the core apoptotic pathway.
Global climate imprint on seismic noise

In the absence of earthquakes, oceanic microseisms are the strongest signals recorded by seismic stations. Using the GEOSCOPE global seismic network, we show that the secondary microseism spectra have global characteristics that depend on the station latitude and on the season. In both hemispheres, noise amplitude is larger during local winter, and close to the equator, noise amplitude is stable over the year. There is an excellent correlation between microseism amplitude variations over the year and changes in the highest wave areas. Considering the polarization of the secondary microseisms, we show that stations in the Northern Hemisphere and close to the equator record significant changes of the secondary microseism source azimuth over the year. During Northern Hemisphere summer, part or all of the sources are systematically located farther toward the south than during winter. Stations in French Guyana (MPG) and in Algeria (TAM) record microseisms generated several thousand kilometers away in the South Pacific Ocean and in the Indian Ocean, respectively. Thus, secondary microseism sources generated by ocean waves which originate in the Southern Hemisphere can be recorded by Northern Hemisphere stations when local sources are weak. We also show, considering a station close to Antarctica, that primary and secondary microseism noise amplitudes are strongly affected by changes of the sea ice floe and that sources of these microseisms are in different areas. Microseism recording can therefore be used to monitor climate changes.
Potential role of cbfa1, an essential transcriptional factor for osteoblast differentiation, in osteoclastogenesis: regulation of mRNA expression of osteoclast differentiation factor (ODF).

The role of Cbfa1 (core binding factor alpha1), an essential transcriptional factor for osteoblast differentiation, in osteoclastogenesis was investigated in vitro and in vivo using Cbfa1-deficient calvarial cells and mice. Co-cultures of calvarial cells isolated from embryos with three different Cbfa1 genotypes (Cbfa1+/+, Cbfa1+/- and Cbfa1-/-) and normal spleen cells generated TRAP-positive multinucleated osteoclast-like cells (OCLs) in response to 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and dexamethasone, but the number and bone-resorbing activity of OCLs formed in co-culture with Cbfa1-/- calvarial cells were significantly decreased in comparison with those formed in co-cultures with Cbfa1+/+ or Cbfa1+/- calvarial cells. The expression of osteoclast differentiation factor/osteoprotegerin ligand (ODF/OPGL) mRNA was increased by the treatment with 1alpha, 25(OH)2D3 and dexamethasone in calvarial cells from Cbfa1+/+ and Cbfa1+/- mouse embryos, but not from Cbfa1-/- embryos. In contrast, the expression of osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) mRNA was inhibited by 1alpha,25(OH)2D3 and dexamethasone similarly in all three types of calvarial cells. ODF/OPGL and OPG/OCIF mRNAs were highly expressed in the tibia and femur of Cbfa1+/+ and Cbfa1+/- embryos. In the tibia and femur of Cbfa1-/- embryos, however, ODF/OPGL mRNA was undetectable and the expression of OPG/OCIF mRNA was also decreased compared with those in Cbfa1+/+ and Cbfa1+/- embryos. These results suggested that Cbfa1 is somehow involved in osteoclastogenesis through regulation of ODF/OPGL.