Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Changes in the L‐Type Calcium Current on Hysteresis in Restitution of Action Potential Duration

Background : Electrical restitution and memory of action potential duration (APD) are considered key determinants of stability of activation. Calcium handling also impacts stability of activation via its modification of the above and independently. We determined the effects of reduction in an important calcium current, ICaL, on hysteresis in restitution of APD, which provides assessment of restitution and memory.
Ets‐1 regulates angiogenesis by inducing the expression of urokinase‐type plasminogen activator and matrix metalloproteinase‐1 and the migration of vascular endothelial cells

The coordinate induction of protease activities and cell migration is a principal feature of endothelial cells (ECs) invading the interstitial space in the initial step of angiogenesis. However, the molecular mechanisms of these events are not fully characterized. Ets‐1 is a member of the ets gene family of transcription factors, which binds to the Ets binding motif in the cis‐acting elements and regulates the expression of certain genes. Four typical angiogenic growth factors, aFGF, bFGF, VEGF, and EGF, induced the expression of ets‐1 mRNA in either human umbilical vein endothelial cells (HUVECs), ECV‐304 cells (immortalized HUVECs), or human omental microvascular endothelial cells (HOMECs). The expression of ets‐1 reached its maximum at 2 hr after factor addition and then decreased to the basal level by 12 hr. For characterization of the role of Ets‐1 in angiogenesis, ets‐1 antisense and sense oligodeoxynucleotides (ODNs) were constructed. The ets‐1 antisense ODN but not sense ODN efficiently blocked the synthesis of Ets‐1 protein by human ECs in response to angiogenic growth factors. Moreover, the ets‐1 antisense ODN but not sense ODN almost completely abolished the binding of endothelial cell extract to DNA containing the Ets binding motif. The expression of urokinase‐type plasminogen activator and matrix metalloproteinase‐1 and the migration of ECs in response to growth factors were significantly inhibited by ets‐1 antisense ODN but not by sense ODN. Tube formation by HOMECs in type 1 collagen gel stimulated with EGF was abrogated by ets‐1 antisense ODN. Finally, the expression of Ets‐1 protein in ECs during angiogenesis in vivo was confirmed by an immunohistochemical analysis using a murine angiogenesis model. These results indicate that the induction of ets‐1 mRNA is a mutual phenomenon in ECs stimulated with angiogenic growth factors. Ets‐1 appears to play an important role in angiogenesis, regulating the expression of proteases and the migration of ECs. © 1996 Wiley‐Liss, Inc.
Studies in subjects with long-term nonprogressive human immunodeficiency virus infection.

BACKGROUND In a small percentage of persons infected with human immunodeficiency virus type 1 (HIV-1), there is no progression of disease and CD4+ T-cell counts remain stable for many years. Studies of the histopathological, virologic, and immunologic characteristics of these persons may provide insight into the pathogenic mechanisms that lead to HIV disease and the protective mechanisms that prevent progression to overt disease. METHODS AND RESULTS We studied 15 subjects with long-term nonprogressive HIV infection and 18 subjects with progressive HIV disease. Nonprogressive infection was defined as seven or more years of documented HIV infection, with more than 600 CD4+ T cells per cubic millimeter, no antiretroviral therapy, and no HIV-related disease. Lymph nodes from the subjects with nonprogressive infection had significantly fewer of the hyperplastic features, and none of the involuted features, characteristic of nodes from subjects with progressive disease. Plasma levels of HIV-1 RNA and the viral burden in peripheral-blood mononuclear cells were both significantly lower in the subjects with nonprogressive infection than in those with progressive disease (P = 0.003 and P = 0.015, respectively). HIV could not be isolated from the plasma of the former, who also had significantly higher titers of neutralizing antibodies than the latter. There was viral replication, however, in the subjects with nonprogressive infection, and virus was consistently cultured from mononuclear cells from the lymph nodes. In the lymph nodes virus "trapping" varied with the degree of formation of germinal centers, and few cells expressing virus were found by in situ hybridization. HIV-specific cytotoxic activity was detected in all seven subjects with nonprogressive infection who were tested. CONCLUSIONS In persons who remain free of disease for many years despite HIV infection the viral load is low, but viral replication persists. Lymph-node architecture and immune function appear to remain intact.
Idiopathic Toe Walking: A Kinematic and Kinetic Profile

Purpose: The differential diagnosis in children who walk on their toes includes mild spastic diplegia and idiopathic toe walking (ITW). A diagnosis of ITW is often one of exclusion. To better characterize the diagnosis of ITW, quantitative gait analysis was utilized in a series of patients with an established diagnosis of ITW. Study Design: Patients with an established diagnosis of ITW were analyzed by quantitative gait analysis. Data were recorded as each subject walked in a self-selected toe-walking pattern. The subject was then asked to ambulate making every effort to walk in a normal heel-toe reciprocating fashion. Data were collected to determine if this group of idiopathic toe walkers was able to normalize their gait. Datasets were compared with each other and with historical normal controls. Results: Fifty-one neurologically normal children (102 extremities) with ITW were studied in the Motion Analysis Laboratory at a mean age of 9.3 years. In the self-selected trials, significant deviations in both kinematics and kinetics at the level of the ankle were identified. Disruption of all 3 ankle rockers and a plantar flexion bias of the ankle throughout the gait cycle were most commonly seen. When asked to attempt a normal heel-toe gait, 17% of the children were able to normalize both stance and swing variables. In addition, 70% were able to normalize some but not all of the stance and swing variables. Conclusion: Quantitative gait analysis is an effective tool for differentiating mild cerebral palsy from ITW. Kinematic and kinetic distinctions between the diagnoses are evident at the knee and ankle. The ability to normalize on demand at least some of the kinematic and kinetic variables associated with toe walking is seen in most children with ITW.
Lifestyle habits and fatigue among people with systemic lupus erythematosus and matched population controls

Objective The objective of this paper is to identify clusters of fatigue in patients with systemic lupus erythematosus (SLE) and matched controls, and to analyze these clusters with respect to lifestyle habits, health-related quality of life (HRQoL), anxiety and depression. Methods Patients with SLE (n = 305) and age- and gender-matched population controls (n = 311) were included. Three measurements of fatigue (Fatigue Severity Scale (FSS), Vitality (VT, from SF-36) and Multidimensional Assessment of Fatigue scale (MAF) and hierarchic cluster analysis were used to define clusters with different degrees of fatigue. Lifestyle habits were investigated through questionnaires. HRQoL was assessed with the SF-36 and anxiety/depression with the Hospital Anxiety and Depression Scale. Results Three clusters, denominated “High,” “Intermediate” and “Low” fatigue clusters, were identified. The “High” contained 80% patients, and 20% controls (median; VT 25, FSS 5.8, MAF 37.4). These had the most symptoms of depression (51%) and anxiety (34%), lowest HRQoL (p < 0.001) and they exercised least frequently. The “Intermediate” (48% patients and 52% controls) (median; VT 55, FSS 4.1, MAF 23.5) had similarities with the “Low” regarding sleep/rest whereas social status and smoking were closer to the “High. ” The“Low” contained 22% patients and 78% controls (median; VT 80, FSS 2.3, MAF 10.9). They had the highest perceived HRQoL (p < 0.001), least symptoms of anxiety (10%), no depression, smoked least (13%) and reported the highest percentage (24%) of exercising ≥3 times/week. Conclusion Fatigue is common, but not a general feature of SLE. It is associated with depression, anxiety, low HRQoL and less physical exercise. Patients with SLE and population controls with a healthy lifestyle reported lower levels of fatigue. Whether lifestyle changes can reduce fatigue, which is a major problem for a majority of SLE patients, needs to be further explored.
Epidemiology of painful procedures performed in neonates: A systematic review of observational studies

Procedural pain in neonates has been a concern in the last two decades. The purpose of this review was to provide a critical appraisal and a synthesis of the published epidemiological studies about procedural pain in neonates admitted to intensive care units. The aims were to determine the frequency of painful procedures and pain management interventions as well as to identify their predictors.
Stable α-Synuclein Oligomers Strongly Inhibit Chaperone Activity of the Hsp70 System by Weak Interactions with J-domain Co-chaperones*

α-Synuclein aggregation and accumulation in Lewy bodies are implicated in progressive loss of dopaminergic neurons in Parkinson disease and related disorders. In neurons, the Hsp70s and their Hsp40-like J-domain co-chaperones are the only known components of chaperone network that can use ATP to convert cytotoxic protein aggregates into harmless natively refolded polypeptides. Here we developed a protocol for preparing a homogeneous population of highly stable β-sheet enriched toroid-shaped α-Syn oligomers with a diameter typical of toxic pore-forming oligomers. These oligomers were partially resistant to in vitro unfolding by the bacterial Hsp70 chaperone system (DnaK, DnaJ, GrpE). Moreover, both bacterial and human Hsp70/Hsp40 unfolding/refolding activities of model chaperone substrates were strongly inhibited by the oligomers but, remarkably, not by unstructured α-Syn monomers even in large excess. The oligomers acted as a specific competitive inhibitor of the J-domain co-chaperones, indicating that J-domain co-chaperones may preferably bind to exposed bulky misfolded structures in misfolded proteins and, thus, complement Hsp70s that bind to extended segments. Together, our findings suggest that inhibition of the Hsp70/Hsp40 chaperone system by α-Syn oligomers may contribute to the disruption of protein homeostasis in dopaminergic neurons, leading to apoptosis and tissue loss in Parkinson disease and related neurodegenerative diseases.
Are postsynaptic 5-HT1A receptors involved in the anxiolytic effects of 5-HT1A receptor agonists and in their inhibitory effects on the firing of serotonergic neurons in the rat?

Previous studies have shown that injection of 5-hydroxytryptamine (serotonin) receptor agonists in the dorsal raphe nucleus (DRN) to stimulate somatodendritic 5-HT1A autoreceptors or in the hippocampus to stimulate postsynaptic 5-HT1A receptors, induces anxiolytic-like effects in the rat. The mechanisms triggered by the latter treatment were investigated by measuring both the electrical activity of serotonergic DRN neurons and the anxiolytic response in rats receiving injections with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) or ipsapirone into the dorsal hippocampus. Anxiety-related behavior was estimated by recording the time of ultrasonic vocalization (USV) due to electric foot shocks under standardized conditions. Intrahippocampal application of 8-OH-DPAT or ipsapirone produced a dose-dependent inhibition of the firing of serotonergic DRN neurons and of the shock-induced USV response. However, the range of efficient doses of 8-OH-DPAT via the intrahippocampal route (1-10 micrograms/rat) was larger than that using the i.v. route of injection (0.15-2.5 micrograms/rat). Furthermore, maximal inhibition of the firing of DRN serotonergic neurons occurred earlier when 8-OH-DPAT was injected i.v. (within 1-2 min) than when it was injected into the dorsal hippocampus (within 5 min). Interestingly, the injection of 8-OH-DPAT into the striatum, where 5-HT1A receptors are hardly detectable, or a lateral ventricle, also yielded dose-dependent reduction in both the firing rate of serotonergic DRN neurons and the USV response. Finally, local lesion with ibotenic acid to eliminate postsynaptic 5-HT1A receptors did not alter the inhibitory effects of intrahippocampal application of 8-OH-DPAT on the firing of serotonergic DRN neurons and the USV response. These data indicated that postsynaptic 5-HT1A receptors were not responsible for the inhibitory effects of 8-OH-DPAT and ipsapirone injected in forebrain areas on the electrical activity of serotonergic neurons and the USV response in rats. As shown by the autoradiographic labeling by [3H]8-OH-DPAT at distance from its injection site in the dorsal hippocampus, the diffusion of 5-HT1A receptor agonists (from injected areas in the forebrain to the DRN where they directly inhibit the electrical activity of serotonergic neurons) more likely accounted for their anxiolytic-like effects.
Comparison of PCDD/F and dl-PCB levels in Turkish foodstuffs: industrial versus rural, local versus supermarket products, and assessment of dietary intake

Polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs) and dioxin-like and non-dioxin-like (indicator) polychlorinated biphenyls (PCBs) were monitored in various foodstuffs of animal origin and edible oil samples obtained from two different cities in Turkey both rural and industrial. Total dioxin+dioxin-like PCBs and indicator PCB concentrations of pooled samples ranged 0.20–4.19 pg World Health Organization-Toxic Equivalency (WHO-TEQ)(1998)/g fat and 57.2–1710 pg/g fat, respectively. The dominant congeners were 2,3,4,7,8-PeCDF, 1,2,3,7,8-PeCDD, 2,3,7,8-TCDD and PCB126. Dietary intake of dioxin+dioxin-like PCBs and indicator PCBs from fish, dairy products, edible oil, egg and meat was 0.509 pg WHO-TEQ1998/kg bw (body weight)/day and 839 pg/kg bw/day in Afyon and 0.588 pg WHO-TEQ1998/ kg bw/day and 1070 pg/kg bw/day in Kocaeli, respectively. The major contributors to total exposure were dairy products and fish. Despite the unexplained high contamination level in an individual egg sample from Kocaeli, average concentration levels in Turkey, even in industrialized regions, were low compared to reported concentrations in Western Europe. Exposure levels were well below the tolerable daily intake (TDI) of 2 pg WHO-TEQ1998/kg body weight.
Melatonin Rhythms in Mice: Role in Autoimmune and Lymphoproliferative Diseases

Abstract: Production of melatonin (MLT) in the pineal gland (PG) of inbred mice such as C57BI/6J, BALB/c, and AKR strains is still a matter of debate. In a recent study we validated the presence of MLT in the PG of these inbred mice. We found a short‐term MLT peak in the middle of the dark period with a pattern that mirrors that found previously in the serum. In another study, based on the known immunoregulatory role of MLT, we investigated the role of the PG and MLT in autoimmune diabetes mellitus type I using, as an experimental model, female nonobese diabetic (NOD) mice. Mice were pinealectomized or treated chronically with MLT (injected subcutaneously or administered via drinking water). We found that neonatal pinealectomy accelerates the development of disease in female NOD mice, whereas exogenous MLT protects animals. This is in spite of the fact that MLT increased the production of insulin autoantibodies (IAA). We conclude that PG and MLT influence the development of autoimmune diabetes, although the mechanism of action needs further investigation.
Effects of vegetation cover of natural grassland on runoff and sediment yield in loess hilly region of China.

BACKGROUND The effects of vegetation cover (VC) on runoff and sediment yield were investigated from rainfall simulation experiments in the Loess Plateau of China. Five VCs from 0% to 80% and three different rainfall intensities (I₂.₀, ₁.₅, ₀.₇₅) were implemented. RESULTS The results indicated that runoff and sediment yields in slopes were significantly affected by I and VC, and when the VC amounted to 40% there occurred obvious benefits of runoff and sediment reductions and then amplitude decreased with the increase of VC. The runoff reduction benefits at I₁. ₅ and I₀. ₇₅ were much greater than that at I₂. ₀, while the sediment reduction benefits had no significant difference among different rainfall intensities. At I₂. ₀, the natural grassland slopes with high VC exhibited the characteristics of high runoff but low sediment production. There existed a power function relationship between cumulative runoff and sediment yield. The increase in cumulative sediment yield was less than the increase in cumulative runoff with increasing VC, and the sediment reduction benefit was greater than runoff reduction on natural grassland slopes. CONCLUSION The ratio of runoff reduction to sediment reduction can be used as a comprehensive index for assessing the benefits of runoff and sediment reduction in natural grassland.
A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits

A novel protein complex has been identified in human cells that has a molecular mass of approximately 450 kDa. It consists of at least eight different subunits including JAB1, the Jun activation‐domain binding protein 1, and Trip15, the thyroid hormone receptor‐interacting protein 15. The purified complex contains COP9 and COP11 protein homologs and is very similar, if not identical, to the plant COP9 complex involved in light‐mediated signal transduction. The isolated JAB1‐containing particle has kinase activity that phosphorylates IκBα, the carboxy terminus of p105, and Ser63 and/or Ser73 of the amino‐terminal activation domain of c‐Jun. The phosphorylation of c‐Jun requires the carboxy terminus of the protein containing the DNA binding and dimerization domains. Three subunits of the new complex—Sgn3, Sgn5/JAB1, and Sgn6—exhibit sequence similarities to regulatory components of the 26S proteasome, which could indicate the existence of common substrate binding sites. Immunofluorescence staining reveals that the new complex shows a subcellular distribution similar to that of the 26S proteasome. The functional relationship of the two particles in regulating transcriptional activity is discussed. Considering the putative role of the complex in signal transduction and its widespread occurrence, we suggest the name JAB1‐containing signalosome. —Seeger, M. , Kraft, R. , Ferrell, K. , Bech‐Otschir, D. , Dumdey, R. , Schade, R. , Gordon, C. , Naumann, M. , Dubiel, W. A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. FASEB J. 12, 469–478 (1998)
Ontogeny and Nutritional Status Influence Oxidative Kinetics of Nutrients and Whole-Animal Bioenergetics in Zebra Finches, Taeniopygia guttata: New Applications for 13C Breath Testing

Rapidly growing animals or those that are recovering from nutritional stress may use exogenous nutrients differently from well fed adults. To test this possibility, we compared the rates of exogenous nutrient oxidation among fledgling, fasted adult, and refed adult zebra finches using a technique called breath testing, where animals are fed 13C-labeled nutrients and 13C in the exhaled breath is collected and quantified. In order to identify the possible mechanisms responsible for differences in oxidative kinetics of ingested nutrients, we also compared body mass (mb), organ mass, core body temperature (Tb), and metabolic rate (MR). We found that fasted birds had lower Tb, relative liver and intestine masses, MR, and respiratory exchange ratios (RERs) than fed adults. Adult birds recovering from nutritional stress had much lower rates of exogenous nutrient oxidation than fed birds; this difference was particularly evident for fatty acids. Differences in oxidative kinetics were correlated with reduced RER, mb, and liver mass, suggesting that previously fasted birds were using recently assimilated nutrients to replenish exhausted fuel stores. Rapidly growing fledglings oxidized exogenous nutrients as quickly as fed adults, despite their significantly lower mb and Tb. We suggest that fledglings had higher mass-specific rates of exogenous nutrient oxidation because they must compensate for the relatively low conversion efficiency of feather production and other lean tissue growth, which was not taking place in the adults. Although this study demonstrates that ontogeny and nutritional status influence the way that birds oxidize exogenous nutrients, it also underscores the likelihood that environmental and endogenous factors shape how other types of animals spend the nutrients they ingest.
Metastatic Tumor Volume and Extranodal Tumor Extension: Clinical Significance in Patients With Stage II Breast Cancer.

CONTEXT Lymph node status and the number of lymph node (LN) positive for cancer cells are the most important prognostic factors in breast cancer. Extranodal tumor extension (ENTE) has been used as a histopathologic feature to classify patients into high risk versus low risk for local recurrence. However, in the current era of early detection and systemic therapy, the prognostic significance of ENTE is not as well defined in patients with 1 to 3 LNs positive for cancer. OBJECTIVE To determine whether the amount of tumor burden in an axillary dissection or the presence of ENTE provides any additional information regarding patient outcome in patents with 1 to 3 positive LN results. DESIGN Clinical and pathologic factors were identified for 456 patients with breast cancer at the University of Texas MD Anderson Cancer Center, Houston, who had pT1 tumors and 1 to 3 LNs positive for cancer and were treated by mastectomy, with or without postmastectomy radiotherapy, between 1978 and 2007. RESULTS Of the 456 patients, 257 (56.4%), 141 (31.6%), and 58 (12.7%) patients had 1, 2, or 3 positive LN results, respectively. Extranodal tumor extension was present in 99 patients (21.7%) and was absent in the remaining 357 cases (78.3%). Seventy-six patients (16.7%) received radiation therapy. Patients had both worse overall survival time and disease-free survival when ENTE was present, regardless of the amount, as long as the treatment era was not included in the multivariate analysis (pre-2000 versus post-2000). However, ENTE was no longer significant on multivariate analysis when the year of treatment was taken into account. CONCLUSIONS The number of positive LNs remains an important predictor of survival in patients with 1 to 3 positive LN results, but the prognostic significance of ENTE in this cohort of patients has diminished over time.