Miracle-dz/UniFAR-FTUs huggingface dataset:
CD4-Induced Conformational Changes in the Human Immunodeficiency Virus Type 1 gp120 Glycoprotein: Consequences for Virus Entry and Neutralization

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) entry into target cells involves sequential binding of the gp120 exterior envelope glycoprotein to CD4 and to specific chemokine receptors. Soluble CD4 (sCD4) is thought to mimic membrane-anchored CD4, and its binding alters the conformation of the HIV-1 envelope glycoproteins. Two cross-competing monoclonal antibodies, 17b and CG10, that recognize CD4-inducible gp120 epitopes and that block gp120-chemokine receptor binding were used to investigate the nature and functional significance of gp120 conformational changes initiated by CD4 binding. Envelope glycoproteins derived from both T-cell line-adapted and primary HIV-1 isolates exhibited increased binding of the 17b antibody in the presence of sCD4. CD4-induced exposure of the 17b epitope on the oligomeric envelope glycoprotein complex occurred over a wide range of temperatures and involved movement of the gp120 V1/V2 variable loops. Amino acid changes that reduced the efficiency of 17b epitope exposure following CD4 binding invariably compromised the ability of the HIV-1 envelope glycoproteins to form syncytia or to support virus entry. Comparison of the CD4 dependence and neutralization efficiencies of the 17b and CG10 antibodies suggested that the epitopes for these antibodies are minimally accessible following attachment of gp120 to cell surface CD4. These results underscore the functional importance of these CD4-induced changes in gp120 conformation and illustrate viral strategies for sequestering chemokine receptor-binding regions from the humoral immune response.
Personality and the risk of cancer.

BACKGROUND The role of personality in the causation of cancer has been controversial. We examined this question in a large, prospective study. METHODS From June through August 1990, 30 277 residents of Miyagi Prefecture in northern Japan completed a Japanese version of the short form of the Eysenck Personality Questionnaire-Revised and a questionnaire on various health habits. There were 671 prevalent cases of cancer at baseline, and 986 incident cases of cancer were identified during 7 years of follow-up, through December 1997. We used Cox proportional hazards regression to estimate the relative risk (RR) of incident cancer (total, stomach, colorectal, breast, and lung) according to four levels of each of four personality subscales (extraversion, neuroticism, psychoticism, and lie), with adjustment for sex, age, education, smoking, alcohol use, body mass index, and family history of cancer. Statistical tests were two-sided. RESULTS Multivariable RRs of total cancer for individuals in the highest level of each personality subscale as compared with those in the lowest were 0.9 for extraversion (95% confidence interval [CI] = 0.7 to 1.1; P(trend) =. 32), 1.1 for psychoticism (95% CI = 0.9 to 1.3; P(trend) =. 96), 0.9 for lie (95% CI = 0.7 to 1.0; P(trend) =. 19), and 1.2 for neuroticism (95% CI = 1.0 to 1.4; P(trend) =. 06). There were no associations between any personality subscale and risk of specific cancers. Neuroticism showed statistically significant positive, linear associations with prevalent cancer at baseline (P(trend)<. 001) and with the 320 incident cancer cases diagnosed within the first 3 years of follow-up (P(trend) =. 03); however, it showed no association with the 666 cases diagnosed during the fourth through the seventh years of follow-up (P(trend) =. 43). CONCLUSION Our data do not support the hypothesis that personality is a risk factor for cancer incidence. The association between neuroticism and prevalent cancer may be a consequence, rather than a cause, of cancer diagnosis or symptoms.
Karcher means and Karcher equations of positive definite operators

The Karcher or least-squares mean has recently become an important tool for the averaging and studying of positive definite matrices. In this paper we show that this mean extends, in its general weighted form, to the infinite-dimensional setting of positive operators on a Hilbert space and retains most of its attractive properties. The primary extension is via its characterization as the unique solution of the corresponding Karcher equation. We also introduce power means Pt in the infinite-dimensional setting and show that the Karcher mean is the strong limit of the monotonically decreasing family of power means as t → 0+. We show that each of these characterizations provide important insights about the Karcher mean.
Enhanced phagocytic response of macrophages to bacteria by physical impact caused by bacterial motility or centrifugation

The mechanism of enhanced phagocytic and chemiluminescent responses of macrophages caused by bacterial motility (T. Tomita, E. Blumenstock, and S. Kanegasaki, Infect. Immun. 32:1242, 1981) was studied. Both responses increased up to a certain level with an increased number of motile bacteria, such as Salmonella typhimurium, Escherichia coli, or Pseudomonas aeruginosa, added. In contrast, only a slight increase was observed with the motility (mot) mutants of these bacteria, even when 4,000 bacteria per single macrophage were added. If nonmotile bacteria were centrifuged together with a monolayer culture of macrophages, the number of bacteria ingested per macrophage increased dramatically. This phenomenon was not observed in the presence of cytochalasin B or at a low temperature, and about half of the associated bacteria were killed within 30 min of prolonged incubation, indicating that the bacteria were not simply embedded on the macrophage surface. An observed biphasic increase of ingestion with an increase in centrifugal force suggested the existence of a threshold velocity for efficient phagocytosis. The minimum centrifugal force required for maximal response was determined under the conditions in which equalized collision frequency between bacteria and macrophages was maintained when different centrifugal forces were employed. From the value obtained (5 x g), the required rate of movement was calculated as approximately 2.5 microns/s, supposing that the bacterium is spherical and has a 1-micron radius. This value is much lower than the velocity of movement of motile bacteria (20 to 50 microns/s). The results indicate that physical impact caused by bacterial motility is enough to induce a high response of macrophages.
Glycine receptor subunit composition alters the action of GABA antagonists

GABA receptor antagonists produce an unexpectedly significant inhibition of native glycine receptors in retina and in α1 or α2 homomeric glycine receptors (GlyRs) expressed in HEK 293 cells. In this study we evaluate this phenomenon in heteromeric glycine receptors, formed by mixing α1, α2, and β subunits. Picrotoxinin, picrotin, SR95531, and bicuculline are all more effective antagonists at GlyRs containing α2 subunits than α1 subunits. Inclusion of β subunits reduces the inhibitory potency of picrotoxinin and picrotin but increases the potency of SR95531 and bicuculline. As a result of these two factors, bicuculline is particularly poor at discriminating GABA and glycine receptors. Picrotin, which has been reported to be inactive at GABA receptors, blocks glycine currents in retina and in HEK293 cells, suggesting its utility as a selective glycine antagonist. However, picrotin is a more potent inhibitor of GABA than glycine in retinal neurons. We also tested if GABA and glycine receptor subunits can combine to form functional receptors. If GABAAR γ2S subunits are co-expressed with GlyR α subunits, the mixed receptor is glycine-sensitive and GABA-insensitive. But the mixed receptor exhibits a non-competitive picrotoxinin inhibition that is not observed in the homomeric GlyRs. This suggests that glycine and GABA subunits can co-assemble to form functional glycine receptors.
Positron emission tomography with α‐[11C]methyl‐l‐tryptophan in tuberous sclerosis complex–related epilepsy

Tuberous sclerosis complex (TSC) is often associated with cerebral tubers and medically intractable epilepsy. We reevaluated whether increased uptake of α‐[11C]methyl‐l‐tryptophan (AMT) in cerebral tubers is associated with tuber epileptogenicity.
Escherichia coli Division Inhibitor MinCD Blocks Septation by Preventing Z-Ring Formation

ABSTRACT The min system spatially regulates division through the topological regulation of MinCD, an inhibitor of cell division. MinCD was previously shown to inhibit division by preventing assembly of the Z ring (E. Bi and J. Lutkenhaus, J. Bacteriol. 175:1118–1125, 1993); however, this was questioned in a recent report (S. S. Justice, J. Garcia-Lara, and L. I. Rothfield, Mol. Microbiol. 37:410–423, 2000) which indicated that MinCD acted after Z-ring formation and prevented the recruitment of FtsA to the Z ring. This discrepancy was due in part to alternative fixation conditions. We have therefore reinvestigated the action of MinCD and avoided fixation by using green fluorescent protein (GFP) fusions to division proteins. MinCD prevented the localization of both FtsZ-GFP and ZipA-GFP, consistent with it preventing Z-ring assembly. Consistent with a direct interaction between FtsZ and the MinCD inhibitor, we find that increased FtsZ, but not FtsA, suppresses MinCD-induced lethality. Furthermore, strains carrying various alleles offtsZ, selected on the basis of resistance to the inhibitor SulA, displayed variable resistance to MinCD. These results are consistent with FtsZ as the target of MinCD and confirm that this inhibitor prevents Z-ring assembly.
Petrology and geochemistry of granulite xenoliths from Udachnaya and Komsomolskaya kimberlite pipes, Siberia

Lower crustal xenoliths from the Udachnaya and Komsomolskaya kimberlite pipes in Siberia are mainly meta-igneous mafic garnet granulites, with subordinate feldspar-rich garnet granulites. Pressure and temperature estimates are interpreted as the conditions in the lower crust at the time of the last granulite-facies metamorphic event (800–890°C) followed by cooling to 610–720°C with a pressure decrease from 1·2 to 0·8 GPa. Most of the xenoliths show minor alteration. Leaching experiments demonstrate that their isotopic, major and trace element compositions have been affected by interaction not only with the host kimberlite but also with a fluid mobilized from local sedimentary country rocks. To obtain unambiguous compositional data we have calculated the composition of selected samples using modal analyses, electron microprobe and laser ablation inductively coupled plasma mass spectrometry data for constituent minerals. The reconstructed protoliths of most of the xenoliths were Fe-tholeiites of intraplate affinity, similar to some Archean basalts, whereas the others show characteristics of subduction-related magmas. However, the mafic granulites are strongly depleted in Rb, Th and U, which were removed by a small-degree partial melt. A protolith age of c. 3 Ga is supported by a disturbed Sm–Nd isochron, Nd and Hf model ages, and published U–Pb ages of zircon cores.
High-Fat Foods and the Risk of Lung Cancer

We conducted a population-based case-control study of the association of dietary cholesterol and fat with lung cancer between 1983 and 1985 on Oahu, Hawaii. The study population included 226 men and 100 women with lung cancer, and 597 male and 268 female community controls matched for age (±5 years) and sex. There was a positive dose-response relation between the consumption of processed meats (luncheon meats, bacon, sausage), dairy foods (whole milk, regular ice cream), eggs, and particular desserts (fruit pies, custard/cream pies) and the risk of lung cancer in men. We also found a positive trend in the risk of lung cancer in women with increasing intake of some processed meats (bacon, Spam) and desserts (cakes, custard/cream pies). The dose-response relation tended to be stronger among men who were heavy smokers and who were diagnosed with squamous cell cancer of the lung. A positive trend in risk was found for nitrite intake in men and dimethylnitrosamine intake in men and women. These data indicate that smokers with a high intake of foods rich in fat and animal protein or who have a preference for cured meats are at increased risk of lung cancer. (Epidemiology 1992;3:288–299)
A histological evaluation on osteogenesis and resorption of methotrexate-loaded calcium phosphate cement in vivo

In this study, we investigated the resorption of in vivo methotrexate-loaded calcium phosphate cement (MTX-CPC) implants and their effect on osteogenesis. MTX-CPC implants containing 1% methotrexate (MTX) (weight/weight) were preset and implanted into the femoral condyle of rabbits. Calcium phosphate cement (CPC) without MTX was used as the control. The femurs were harvested at day 1 and at 1, 3 and 6 months after implantation and radiological examination were performed. Decalcified sections were examined by hematoxylin and eosin (HE) staining, alkaline phosphatase (ALPase) immunohistochemistry and tartrate-resistant acid phosphatase (TRAPase) enzyme histochemistry. Then, we performed histomorphometric analysis, including determination of the percentage of newly formed bone and osteoblast and osteoclast counts. The results indicated that MTX-CPC implants were biocompatible, biodegradable and osteoconducive. However, MTX release from the implantation site inhibited osteogenesis in the initial period; this inhibition weakened with time, and no difference was observed between CPC and MTX-CPC at 6 months after implantation. Hence, MTX-CPC is an excellent material for filling defects and can be used for preparing effective drug delivery systems to achieve local control of invasive bone tumors.
Overweight and obesity in 6- to 14-year-old Czech children in 1991: protective effect of breast-feeding.

OBJECTIVE To assess the impact of breast-feeding on childhood overweight/obesity in an Eastern European socialist society with relatively homogeneous lifestyles. STUDY DESIGN Cross-sectional survey data collected in 1991 on 33,768 school-children aged 6 to 14 years in the Czech Republic were analyzed by using multiple logistic regression analyses (main outcome body mass index [BMI] >90th percentile [overweight] and BMI >97th percentile [obesity]). RESULTS Overall prevalence of overweight (obesity) was lower in breast-fed children: ever breast-fed (9.3%; 95% CI, 8.9-9.6 [3.2%; 95% CI, 3.0-3.4]) compared with never breast-fed (12.4%; 95% CI, 11.3-13.6 [4.4%; 95% CI, 3.7-5.2]). The effect of breast-feeding on overweight/obesity did not diminish with age in children 6 to 14 years old and could not be explained by parental education, parental obesity, maternal smoking, high birth weight, watching television, number of siblings, and physical activity. Adjusted odds ratios for breast-feeding were for overweight 0.80 (95% CI, 0.71-0.90) and for obesity 0.80 (95% CI, 0.66-0.96). CONCLUSIONS A reduced prevalence of overweight/obesity was associated with breast-feeding in a setting where socioeconomic status was homogeneous. This suggests that the effect of breast-feeding on the prevalence of obesity is not confounded by socioeconomic status.
The Reliability of Estimating Ki Values for Direct, Reversible Inhibition of Cytochrome P450 Enzymes from Corresponding IC50 Values: A Retrospective Analysis of 343 Experiments

In the present study, we conducted a retrospective analysis of 343 in vitro experiments to ascertain whether observed (experimentally determined) values of Ki for reversible cytochrome P450 (P450) inhibition could be reliably predicted by dividing the corresponding IC50 values by two, based on the relationship (for competitive inhibition) in which Ki = IC50/2 when [S] (substrate concentration) = Km (Michaelis-Menten constant). Values of Ki and IC50 were determined under the following conditions: 1) the concentration of P450 marker substrate, [S], was equal to Km (for IC50 determinations) and spanned Km (for Ki determinations); 2) the substrate incubation time was short (5 minutes) to minimize metabolism-dependent inhibition and inhibitor depletion; and 3) the concentration of human liver microsomes was low (0.1 mg/ml or less) to maximize the unbound fraction of inhibitor. Under these conditions, predicted Ki values, based on IC50/2, correlated strongly with experimentally observed Ki determinations [r = 0.940; average fold error (AFE) = 1.10]. Of the 343 predicted Ki values, 316 (92%) were within a factor of 2 of the experimentally determined Ki values, and only one value fell outside a 3-fold range. In the case of noncompetitive inhibitors, Ki values predicted from IC50/2 values were overestimated by a factor of nearly 2 (AFE = 1.85; n = 13), which is to be expected because, for noncompetitive inhibition, Ki = IC50 (not IC50/2). The results suggest that, under appropriate experimental conditions with the substrate concentration equal to Km, values of Ki for direct, reversible inhibition can be reliably estimated from values of IC50/2.
Psychological condition in patients with an acoustic tumor

Abstract Conclusions: This study showed that patients with acoustic tumor (AT) with hearing loss in the contralateral side had severe mood disturbances. It is important for physicians to provide patients who have better hearing in the tumor side with adequate information regarding the possibility of profound bilateral hearing loss and how to communicate with others in such situations. Objectives: We examined the pretreatment status as regards neurosis and/or depression of patients with an AT using the Cornell Medical Index (CMI) and Self-rating Depression Scale (SDS) and clarified the relationship with the patients' background. Methods: We enrolled 30 patients with unilateral AT between 1997 and 2010. At the time of diagnosis, we examined each patient's psychological condition, sex, age, laterality, tumor size, hearing level on bilateral side, facial paresis, headache, and canal paresis. Results: In all, 20.0% of AT patients were diagnosed with neurosis using the CMI and 26.7% had depression according to the SDS. χ2 analysis showed that patients with AT with hearing deterioration on the contralateral side had mental illness significantly more often than those with normal hearing on the contralateral side. Multivariable regression analysis revealed that the pretreatment status of hearing level on the contralateral side significantly affected the patients' psychological condition.
Stable Isotope Analysis in Primatology: A Critical Review

Stable isotope analysis has become an important tool in ecology over the last 25 years. A wealth of ecological information is stored in animal tissues in the relative abundances of the stable isotopes of several elements, particularly carbon and nitrogen, because these isotopes navigate through ecological processes in predictable ways. Stable carbon and nitrogen isotopes have been measured in most primate taxonomic groups and have yielded information about dietary content, dietary variability, and habitat use. Stable isotopes have recently proven useful for addressing more fine‐grained questions about niche dynamics and anthropogenic effects on feeding ecology. Here, we discuss stable carbon and nitrogen isotope systematics and critically review the published stable carbon and nitrogen isotope data for modern primates with a focus on the problems and prospects for future stable isotope applications in primatology. Am. J. Primatol. 74:969‐989, 2012. © 2012 Wiley Periodicals, Inc.
Type 2 diabetes has minimal effect on osseointegration of titanium implants in Psammomys obesus.

OBJECTIVES Dental implants are routinely used with high success rates in generally healthy individuals. In contrast, their use in patients with uncontrolled diabetes mellitus (DM) remains controversial as altered bone healing around implants has been reported. The majority of reports addressing the issue of osseointegration of implants in animals were performed in beta-cell cytotoxic-induced Type I diabetes. In this study, we assessed the osseointegration of implants in Gerbil Psammomys obesus, a model of nutritionally induced Type 2 DM. MATERIALS AND METHODS Titanium implants were inserted into the tibial medullary space of 140 male diabetic and control animals. One, 2, 4, and 8 weeks after implantation the tibias were removed for histomorphometric evaluation, which included trabecular bone volumes (TBV) and osseointegration. RESULTS Two weeks following implantation, diabetic animals had slightly less mature bone when compared with control animals. This distinction was not present 4 weeks after implantation. Interestingly, no correlation was found between ossetointegration or TBV and glucose and insulin levels. Furthermore, no difference in osseointegration and TBV values was seen between the groups. The heterogeneity of serum glucose and insulin levels in this model and the possible role of insulin in bone metabolism are discussed. CONCLUSIONS No significant difference in osseointegration and TBV was seen between diabetic and control P. obesus, a model of nutritionally induced Type 2 DM.
Physiological responses of laying hens during whole-house killing with carbon dioxide

1. Poultry on farms are sometimes required to be killed in an emergency, such as during a disease epidemic, yet none of the available methods are ideal. Whole-house carbon dioxide (CO2) administration has practical advantages, but gives rise to welfare concerns. 2. The study measured the body temperature, respiration, cardiac and brain activity (EEG) responses of 10 adult hens placed in tiered cages in a deep pit house while the entire flock (28,000 end-of-lay hens) was killed with CO2. Video and thermographic images were also recorded. Liquid CO2 was injected into the building producing a gaseous concentration of 45% within 19 min. 3. Those hens nearest the gas delivery site showed delayed respiratory, cardiac and EEG responses compared with those at more distant locations. Although sub-zero temperatures were recorded in the immediate vicinity of some birds, body temperatures indicated that they did not die of hypothermia. 4. EEG characteristics strongly associated with unconsciousness were used to determine an unequivocal time to loss of consciousness; this ranged from 6·0 to 10·5 (average 7·8) min after onset of gas injection. Distinctive cardiac and respiratory responses were seen following gas exposure; in particular, birds responded to inhalation of CO2 by deep breathing. 5. The primary welfare concern is the duration of unpleasant respiratory effects, such as deep breathing, while the birds were substantively conscious. However, the concentration of CO2 to which the birds were exposed while conscious would not have stimulated nasal and oral nociceptors. Time to death varied between 12·0 and 22·1 min after gas delivery.