Miracle-dz/UniFAR-FTUs huggingface dataset:
European starling (Sturnus vulgaris): Avian model and monitor of polychlorinated biphenyl contamination at a Superfund site in Southern Illinois, USA

Accumulation and effects of polychlorinated biphenyls (PCBs) in avian species were evaluated at a Superfund site located at Crab Orchard National Wildlife Refuge (IL, USA). European starlings (Sturnus vulgaris) were monitored at nest boxes constructed at each of two study and two reference sites. During the breeding season, starling productivity and adult provisioning behavior were monitored. At 15 d after hatch, chicks and adults were collected for contaminant and biomarker analyses. Chicks and adults were necropsied, ethoxyresorufin‐O‐deethylase (EROD) activity was measured in liver tissue, and polychlorinated biphenyl (PCB; Aroclor 1254) and 34 chlorinated biphenyl (CB) congener concentrations were measured in carcasses. Polychlorinated biphenyl and CB concentrations also were measured in eggs that failed to hatch. Mean Aroclor 1254 and quantified CB concentrations were greater (p < 0.001) in eggs that failed to hatch, 15‐d‐old chicks, and adults collected from PCB‐contaminated sites (hereafter PCB sites) compared to those collected from reference sites. The EROD activity was greater (p = 0.005) in 15‐d‐old chicks, but not adults (p = 0.972), collected from PCB sites compared to those collected from reference sites. No differences were found among study and reference sites in number of eggs laid or percent of eggs hatched; however, reduced nest provisioning behavior and decreased chick survival were observed at PCB sites. Polychlorinated biphenyl concentrations measured in samples collected from the PCB sites are similar to concentrations previously associated with adverse effects in avian species. Other avian species utilizing these sites also may be exposed to PCBs with associated adverse effects. This study demonstrates that starling nestlings are good biological monitors of local contamination and continued monitoring may provide useful data for evaluating the effectiveness of proposed remediation.
Daily activity recognition system for the elderly using pressure sensors

As transformed to aging society rapidly, the number of old persons who live alone is drastically increased. Because these old people may have disorder of bodily function, and be suffering from geriatric disease, needs of a health assistance system to make them healthier are strongly increased. In this paper, we propose a daily activity recognition system for an old person using pressure sensors. The target daily activities are MEAL, SLEEP, EXCRETION, GO-OUT, and REST. The proposed system installs pressure sensors to furniture and floors in home, and recognizes daily activities based on the object usage information. By using the proposed system, we can provide a warning sign for unhealthy cases such as skipping meals. And, the families who live in remote place can check that their parent takes a healthy daily living.
Site-specific ubiquitination is required for relieving the transcription factor Miz1-mediated suppression on TNF-α–induced JNK activation and inflammation

The transcription factor zinc-finger protein Miz1 represses TNF-α–induced JNK activation and the repression is relieved upon TNF-α stimulation. However, the underlying mechanism is incompletely understood. Here we report that Miz1 interferes with the ubiquitin conjugating enzyme (E2) Ubc13 for binding to the RING domain of TNF-receptor associated factor 2 (TRAF2), thereby inhibiting the ubiquitin ligase (E3) activity of TRAF2 and suppressing TNF-α–induced JNK activation. Upon TNF-α stimulation, Miz1 rapidly undergoes K48-linked polyubiquitination at Lys388 and Lys472 residues and subsequent proteasomal degradation in a TRAF2-dependent manner. Replacement of Lysine 388 and Lysine 472 by arginines generates a nondegradable Miz1 mutant, which significantly suppresses TNF-α–induced JNK1 activation and inflammation. Thus, our results reveal a molecular mechanism by which the repression of TNF-α–induced JNK activation by Miz1 is de-repressed by its own site-specific ubiquitination and degradation, which may account for the temporal control of TNF-α–JNK signaling.
Comparison of Radiofrequency Ablation in Normal Versus Scarred Myocardium

Introduction: Reentrant circuits causing ventricular tachycardia are closely associated with previously scarred myocardium. The presence of scar has been blamed for the poor success rate of radiofrequency ablation (RFA) in that context. This article investigates the in vivo effects of radiofrequency ablation in myocardium scarred from acute myocardial infarction.
ROLE OF ARTERIAL WALL CELLS IN SCLEROGENESIS

Three factors are of decisive importance in the pathogenesis of arteriosclerosis and atherosclerosis: problems of lipid metabolism, problems of blood coagulation, and the function of the arterial wall cells themselves. In the past, much emphasis has been placed on the first two problems, whereas the role of arterial wall cells has received less attention. To understand sclerogenesis, it is essential to study the very beginning of the sclerotic process. In this paper, I shall give evidence to suggest that the reaction of wall cells induced directly by “risk factors” is the first and, moreover, the essential step that initiates arteriosclerosis. This reaction must be recognized as part of the “unspecific mesenchymal reaction,”’ because arterial wall cells belong to the mesenchymal system. ’-‘ Because it is difficult (actually almost impossible) to study the earliest stages of the sclerotic process in man, our knowledge must be supplied by animal experiments. In the past 15 years, we have studied intensively the effect of a variety of atherogenic o r sclerogenic factors in animal models, especially arterial hypertension, sclerogenic diet, infectious diseases, injection of toxins, emotional stress, and electrical stimulation of the hypothalamus. In this paper, 1 shall discuss acceleration of arterial wall cell proliferation, acceleration of arterial wall cell metabolism, and the consequences of wall cell reactions: edema, fibrosis, and hyalinosis of the arterial wall; lipidosis, fibrinosis, and necrosis of the arterial wall; and thrombosis in and on the arterial wall. The space available does not permit me to completely review our experiments, so 1 will provide only some examples.
DDX60, a DEXD/H Box Helicase, Is a Novel Antiviral Factor Promoting RIG-I-Like Receptor-Mediated Signaling

ABSTRACT The cytoplasmic viral RNA sensors RIG-I and MDA5 are important for the production of type I interferon and other inflammatory cytokines. DDX60 is an uncharacterized DEXD/H box RNA helicase similar to Saccharomyces cerevisiae Ski2, a cofactor of RNA exosome, which is a protein complex required for the integrity of cytoplasmic RNA. Expression of DDX60 increases after viral infection, and the protein localizes at the cytoplasmic region. After viral infection, the DDX60 protein binds to endogenous RIG-I protein. The protein also binds to MDA5 and LGP2 but not to the downstream factors IPS-1 and IκB kinase ε (IKK-ε). Knockdown analysis shows that DDX60 is required for RIG-I- or MDA5-dependent type I interferon and interferon-inducible gene expression in response to viral infection. However, DDX60 is dispensable for TLR3-mediated signaling. Purified DDX60 helicase domains possess the activity to bind to viral RNA and DNA. Expression of DDX60 promotes the binding of RIG-I to double-stranded RNA. Taken together, our analyses indicate that DDX60 is a novel antiviral helicase promoting RIG-I-like receptor-mediated signaling.
Anticancer activity of novel unnatural synthetic isoprenoids.

BACKGROUND The KRAS oncogene has a high prevalence in solid malignancies. Targeting KRAS and inappropriate activation of the MAPK pathway with novel drugs is of interest. This study developed and screened a library of compounds designed to inhibit KRAS signaling by altering prenyl function. MATERIALS AND METHODS To screen a library of novel farnesyl analogs for their anticancer activity in human lung cancer and breast cancer cell lines. To evaluate if the designed and actual pharmacology are congruent. RESULTS Sixty-seven novel compounds were tested and 70% of them screened positive for activity in at least one cell line. Two active compounds inhibited phosphorylation of MAP kinase consistent with KRAS inhibition. CONCLUSION Although 47 of the 67 novel agents screened positive for activity, none of them were highly potent. However, targeting RAS with compounds that compete with farnesyl and geranylgeranyl modification of the protein remains viable and further work is already underway to create second generation molecules.
Tumor-associated macrophages promote tumor metastasis via the TGF-β/SOX9 axis in non-small cell lung cancer

Tumor-associated macrophages (TAMs), most of which display the immunosuppressive M2 phenotype, affect the tumor microenvironment and promote progression and metastasis in lung carcinoma. In this study, we analyzed clinical non-small cell lung cancer (NSCLC) samples and found that high densities of TAMs were associated with a poor prognosis in NSCLC patients. Moreover, the number of TAMs present correlated positively with expression of sex determining region Y (SRY)-related high mobility group box 9 (SOX9) in NSCLC tissues. TAMs secreted TGF-β, which increased SOX9 expression and promoted epithelial-to-mesenchymal transition (EMT) in lung cancer cells, thereby promoting tumor proliferation, migration, and invasion. SOX9 knockdown inhibited EMT, indicating that TGF-β-mediated EMT is SOX9-dependent. TGF-β induced SOX9 expression by upregulating the C-jun/SMAD3 pathway. These results indicate that TGF-β secreted by TAMs promotes SOX9 expression via the C-jun/SMAD3 pathway, thereby promoting tumor metastasis. The TGF-β/SOX9 axis may therefore be an effective target for the treatment of lung cancer.
Assessment of articular cartilage thickness of the humeral head: MR-anatomic correlation in cadavers.

OBJECTIVE The purpose of our study was to evaluate several commonly used MR sequences to determine how accurately each demonstrates the thickness of the articular cartilage of the humeral head. MATERIALS AND METHODS Ten cadaveric shoulders (age at death, 58-92 years; mean, 79 years) were imaged with fat-suppressed transaxial T1-weighted spin-echo three-dimensional gradient-recalled sequences, both before and after injection of 12 ml of diluted gadopentetate dimeglumine. Articular cartilage was measured to the nearest 10th of a millimeter on the MR images and corresponding anatomic sections. RESULTS Cartilage could not be differentiated from surrounding structures in 14 of 112 locations (13%) on the spin-echo images obtained without contrast material, in 4 of 112 locations (4%) on the spin-echo images obtained with contrast material, in 4 of 112 locations (4%) on the gradient-echo images obtained without contrast material, and in 6 of 112 locations (5%) on the gradient-echo images obtained with contrast material. Mean true cartilage thickness was 1.23 mm (SD, 0.52 mm). The mean MR-anatomic differences (absolute values) were 0.38 mm for the spin-echo images obtained without contrast material, 0.42 mm for the spin-echo images obtained with contrast material, 0.49 mm for the gradient-echo images obtained without contrast material, and 0.37 mm for the gradient-echo images obtained with contrast material. There was a tendency to overestimate thin cartilage and to underestimate thick cartilage. CONCLUSION Several of the routinely used MR sequences, with and without intraarticular contrast medium, may cause errors in the assessment of the articular cartilage of the humeral head. Some of these errors result from either insufficient contrast between cartilage and surrounding structures or inadequately concentrated contrast medium.
Infection Associated with Tunneled Hemodialysis Catheters

The use of tunneled dialysis catheters to deliver hemodialysis treatment may be associated with major problems. For this reason their use should be minimized as much as possible. Infection is the most serious of these problems. This complication causes very significant morbidity and mortality and has emerged as the primary barrier to long‐term catheter use. Bacteremia is the most serious type of infection associated with catheter use. It can result in metastatic infection and even lead to death of the patient. Prophylaxis is important to decrease the risk of infection. The use of an antibiotic ointment at the exit site until it has healed and the long‐term use of a dressing to cover the exit site are effective in decreasing the incidence of exit‐site infection. With optimal catheter‐use management, it should be possible to reduce the incidence of catheter‐related bacteremia (CRB) to a level in the range of 1/1000 catheter days. Antibiotic and antimicrobial locking solutions show promise and may, if verified in appropriate clinical studies, prove to be important adjuncts to the management of catheter‐dependent patients. Aspirin has been shown to have anti‐staphylococcal activity and warrants further clinical evaluation. The diagnosis of CRB is based upon positive blood cultures in association with typical clinical features. If a simple routine blood culture is positive, along with a high clinical probability based upon the patient’s signs and symptoms, the sensitivity and specificity of the diagnosis is greater than 75%. CRB is in reality a biofilm infection and must be treated as such. Treatment needs to focus on appropriate systemic antibiotics which should be continued for a minimum of 3 weeks and catheter management to remove the biofilm. Catheter exchange has been shown to be effective and should be performed based upon the clinical presentation of the patient. While treatment with a combination of systemic antibiotics and antibiotic locking solution may be effective for gram‐negative infections, this approach does not appear to be a good choice for Staphylococcus aureus CRB.
Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes.

OBJECTIVE To examine by immunohistochemistry the relative distributions of 6 matrix metalloproteinases (MMPs 1, 2, 3, 8, 9, and 13) and the 2 proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) in osteoarthritic (OA) cartilage compared with normal, age-matched articular cartilage. METHODS Articular cartilage samples were obtained from the tibial plateau of OA knees removed at arthroplasty and from normal, nonarthritic, knees obtained at autopsy. Specimens were promptly fixed in Carnoy's fixative, processed, embedded in paraffin, sectioned, and examined by immunohistochemistry for MMP and cytokine production. In addition, human articular chondrocytes (HAC) were treated in vitro with either IL-1beta, TNFalpha, or phorbol myristate acetate (PMA) to assess their potential to produce each of the MMPs, as determined by Western blotting and gelatin zymography. RESULTS Immunodetection of the collagenases (MMPs 1, 8, and 13) and stromelysin 1 (MMP-3) was demonstrated in a proportion of chondrocytes in the superficial zone of almost all of the OA specimens that had degenerative matrix changes. The gelatinases (MMPs 2 and 9) were also demonstrated by immunohistochemistry but were not so prominent. IL-1beta- and TNFalpha-positive chondrocytes were also observed in a proportion of cells in the superficial zones of OA specimens. Much less immunostaining for MMPs and cytokines was observed in the deep zone of all OA specimens, where the cartilage matrix and chondrocyte morphology appeared normal. In contrast, full-thickness normal cartilage specimens showed virtually no immunostaining for these MMPs or cytokines. Confirmation that chondrocytes can produce these 6 MMPs was obtained from HAC cultures treated with either IL-1beta, TNFalpha, or PMA; conditioned medium from activated HAC contained all the MMPs demonstrated by immunohistochemistry. Dual immunolocalization studies of OA cartilage specimens demonstrated the coexpression of IL-1 with MMP-8 by individual chondrocytes in situ. CONCLUSION These results indicate that the superficial zone of OA cartilage specimens, which is characterized by fibrillations, chondrocyte clusters, and degenerative matrix changes, contains a variable proportion of cells that immunostain for IL-1beta, TNFalpha, and 6 different MMPs. These observations support the concept that cytokine-MMP associations reflect a modified chondrocyte phenotype and an intrinsic process of cartilage degradation in OA.
Identification of the DNA binding element of the human ZNF300 protein

The human ZNF300 gene is a member of the KRAB/C2H2 zinc finger gene family, the members of which are known to be involved in various developmental and pathological processes. Here, we show that the ZNF300 gene encodes a 68-kDa nuclear protein that binds DNA in a sequence-specific manner. The ZNF300 DNA binding site, C(t/a)GGGGG(c/g)G, was defined via a random oligonucleotide selection assay, and the DNA binding site was further confirmed by electrophoretic mobility shift assays. A potential ZNF300 binding site was found in the promoter region of the human IL-2Rβ gene. The results of electrophoretic mobility shift assays indicated that ZNF300 bound to the ZNF300 binding site in the IL-2Rβ promoter in vitro. Transient co-transfection assays showed that ZNF300 could activate the IL-2Rβ promoter, and that the activation was abrogated by the mutation of residues in the ZNF300 binding site. Identifying the DNA binding site and characterizing the transcriptional regulation property of ZNF300 would provide critical insights into its potential as a transcriptional regulator.
Developmental time, body size and wing loading in Drosophila buzzatii from lowland and highland populations in Argentina.

Genotype-by-temperature interaction is a necessary condition for adaptive evolution of fitness traits as a response to temperature. Several fitness-related traits (developmental time, pre-adult survival, thorax and wing lengths, and wing loading) were measured in laboratory-reared D. buzzatii from four populations sampled at different altitudes in north-western Argentina: a lowland population (407 m a.s.l.), two populations from intermediate altitude (780 to 950 m a.s.l.), and a highland population (2380 m a.s.l.). Temperature is the main climatic difference between the collection sites: lowland but not highland populations are exposed to physiologically high temperatures during both spring and summer in nature. Three growth temperatures (20, 25 and 30 degrees C) were used to test for population-by-temperature interactions. Both developmental time and pre-adult survival exhibit highly significant population-by-temperature interaction. Pre-adult survival at 30 degrees C is significantly higher in lowland than in highland populations, but not so at lower growth temperatures (20 and 25 degrees C). Both wing length and wing loading show no population-by-temperature interaction, indicating that these traits are not the direct targets of thermal adaptation in nature. Wing loading is higher in highland than in lowland populations, suggesting that flight performance is subject to stronger selection in the highland population. This hypothesis is consistent with ecological observations in both types of populations. There is no obvious among-population relationship between developmental time and body size, even though both traits are related within populations in a well-known trade-off. Overall, thermal adaptation is evident for developmental time and pre-adult survival but not for size-related traits.
Multi-minicore disease: a rare form of myopathy.

BACKGROUND Multi-minicore disease is a rare form of myopathy characterized by slowly progressive or nonprogressive muscle weakness and characteristic multiple cores within the muscle fibers. To the best of our knowledge, this is first documentation of the clinicopathological features of this rare entity from India. MATERIALS AND METHODS A ll cases of multi-minicore disease diagnosed in our laboratory were retrieved. Clinical and pathological features were reviewed. RESULT During a period of two years (January 2004 to December 2005), we received 985 muscle biopsies for various reasons. Of which, 15 were diagnosed as myopathies and four of which were of multi-minicore disease. Thus, multi-minicore disease comprises 0.40% of all muscle diseases and 26.6% of all myopathies. All were male and presented in early childhood (first decade of life) with generalized hypotonia and muscle weakness. All of them had dysmorphic facies and three had high arched palate. CPK levels were normal and EMG was myopathic except in one patient. Microscopic examination revealed minimal changes with Type I fibers' predominance but characteristic multiple cores in the myofibers. Ultrastructural examination showed both structured and unstructured cores. CONCLUSIONS Multi-minicore disease, although a rare form of myopathies, should be suspected in children who present with generalized hypotonia and slowly progressive muscle weakness along with dysmorphic facies.
MicroRNA aberrances in head and neck cancer: pathogenetic and clinical significance

Purpose of reviewMicroRNAs (miRNAs) play crucial roles in modulating the neoplastic process of cancers including head and neck squamous cell carcinoma (HNSCC). miRNAs modulate pathogenesis by inhibiting target genes. Understanding how aberrant miRNAs are involved in HNSCC pathogenesis should help to validate potential clinical applications that target these entities. Recent findingsmiR-21, miR-31, miR-504 and miR-10b are important oncogenic miRNAs that are involved in HNSCC and target tumour suppressor genes. The tumour suppressor roles of the let-7 family, the miR-99 family, miR-107, miR-133a, miR-137, miR-138 and miR-375 with respect to their targeting of oncogenes are unequivocal and have been confirmed by many studies. In addition, miR-21, let-7, miR-107, miR-138 and miR-200c seem to play complicated roles in regulating stemness or the epithelial-mesenchymal transition of tumour cells. The clinical implications of these tumour-associated miRNAs are generally in agreement with their functional roles. SummaryA number of pathways that become disregulated by aberrant miRNAs have been identified specifically for HNSCC. Analysis of these networks and their therapeutic interception might facilitate the prediction of disease status and help with the design of therapeutic trials.
Unmasking the Osteoinductive Effects of a G‐Protein‐Coupled Receptor (GPCR) Kinase (GRK) Inhibitor by Treatment With PTH(1–34)

The effects of GPCR systems in bone are regulated by a family of enzymes termed GRKs. We found that (1) GRK inhibition in osteoblasts has age‐dependent effects on bone mass, and (2) the anabolic actions of GRK inhibition are revealed by treatment with PTH(1–34).