Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure-based virtual screening identifies a small-molecule inhibitor of the profilin 1–actin interaction

Profilin 1 (Pfn1) is an important regulator of the actin cytoskeleton and plays a vital role in many actin-based cellular processes. Therefore, identification of a small-molecule intervention strategy targeted against the Pfn1–actin interaction could have broad utility in cytoskeletal research and further our understanding of the role of Pfn1 in actin-mediated biological processes. Based on an already resolved Pfn1–actin complex crystal structure, we performed structure-based virtual screening of small-molecule libraries to seek inhibitors of the Pfn1–actin interaction. We identified compounds that match the pharmacophore of the key actin residues of Pfn1–actin interaction and therefore have the potential to act as competitive inhibitors of this interaction. Subsequent biochemical assays identified two candidate compounds with nearly identical structures that can mitigate the effect of Pfn1 on actin polymerization in vitro. As a further proof-of-concept test for cellular effects of these compounds, we performed proximity ligation assays in endothelial cells (ECs) to demonstrate compound-induced inhibition of Pfn1–actin interaction. Consistent with the important role of Pfn1 in regulating actin polymerization and various fundamental actin-based cellular activities (migration and proliferation), treatment of these compounds reduced the overall level of cellular filamentous (F) actin, slowed EC migration and proliferation, and inhibited the angiogenic ability of ECs both in vitro and ex vivo. In summary, this study provides the first proof of principle of small-molecule–mediated interference with the Pfn1–actin interaction. Our findings may have potential general utility for perturbing actin-mediated cellular activities and biological processes.
Effects of Skin Surface Cooling and Heating on Autonomic Nervous Activity and Baroreflex Sensitivity in Humans

The influence of skin surface cooling and heating on heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) were studied in 11 healthy supine volunteers in air temperatures of 18°C (cool), 24°C (mild), 48°C (warm), and 60°C (hot) in a styrene foam chamber. The high‐frequency component of HRV (HFRR) decreased and the ratio of low‐ to high‐frequency components, LFRR/HFRR, increased with skin surface heating. Therefore, a suppression of cardiac vagal nervous activity and an enhancement of cardiac sympathetic nervous activity can be caused by skin surface heating. The low‐frequency component of BPV (LFSBP), i.e. the fluctuations of the Mayer waves, increased with skin surface heating. The responses between the very low‐frequency components of HRV (VLFRR) and systolic BPV (VLFSBP) to thermal skin stimulation were different, although these variables both were considered to be indicators of the thermoregulatory vasomotor control or renin‐angiotensin system. Baroreflex sensitivity (BRS) did not increase with skin surface heating, at least in humans.
High-Density Lipoproteins Enhance Progenitor-Mediated Endothelium Repair in Mice

Objective—We quantified endothelial progenitor cell (EPC) engraftment into the endothelial layer as an index of progenitor-mediated endothelial repair. Studies were conducted in C57BL/6J and in apolipoprotein E–deficient (apoE−/−) mice. We also investigated the possibility that high-density lipoproteins (HDL) may promote progenitor-mediated endothelial repair. Methods and Results—Thoracic aortic sections from C57BL/6J and apoE−/− mice were analyzed for evidence of progenitor-derived endothelium as determined by the number of stem cell antigen-1–positive (Sca-1+) cells in the endothelial layer. EPCs (Sca-1+ cells) were significantly increased after endothelial damage induced by lipopolysaccharide (LPS) administration in C57BL/6J mice. The number of EPCs was greater in the aortic endothelium of untreated apoE−/− than in untreated C57BL/6J mice and was similar to the number observed in LPS-treated C57BL/6J mice. The number of EPCs in the aortic endothelium of apoE−/− mice more than doubled after intravenous infusion of reconstituted HDL. Conclusions—EPCs are recruited into the aortic endothelial layer of mice in response to an inflammatory insult. EPCs are also increased in the aortic endothelium of untreated apoE−/− mice. The observation that number is further increased in apoE−/− mice after injection of HDL suggests a role for HDL in promoting progenitor-mediated endothelial repair.
Parasite‐Driven Extinction in Spatially Explicit Host‐Parasite Systems

General host‐parasite theory suggests that parasites may be implicated in the extinction of their hosts by causing instability that leads to increased risk of stochastic extinction. In contrast, spatially explicit models suggest that the parasite may directly drive the host population to extinction. Here we examine the ecological characteristics of host‐parasite interactions that favor parasite‐driven host extinction. Pair approximations and simulations show that parasites only drive their hosts to extinction when they significantly reduce host reproduction. As a matter of interest, parasites that have a relatively small effect on host death rate are more likely to cause host extinction. Parasite‐driven host extinction occurs at any population size, whereas extinction caused by stochastic effects is less likely to occur in large host populations. Populations may therefore be under threat from parasites that stop host reproduction, and this type of parasite may prove to be the most effective biological pesticide.
Mechanisms of atherothrombosis in chronic obstructive pulmonary disease

Patients affected by chronic obstructive pulmonary disease (COPD) have an increased risk of atherothrombotic acute events, independent of smoking and other cardiovascular risk factors. As a consequence, myocardial ischemia is a relevant cause of death in these patients. We reviewed studies concerning the potential mechanisms of atherothrombosis in COPD. Bronchial inflammation spreads to the systemic circulation and is known to play a key role in plaque formation and rupture. In fact, C-reactive protein blood levels increase in COPD and provide independent prognostic information. Systemic inflammation is the first cause of the hypercoagulable state commonly observed in COPD. Furthermore, hypoxia is supposed to activate platelets, thus accounting for the increased urinary excretion of platelet-derived thromboxane in COPD. The potential metabolic risk in COPD is still debated, in that recent studies do not support an association between COPD and diabetes mellitus. Finally, oxidative stress contributes to the pathogenesis of COPD and may promote oxidation of low-density-lipoproteins with foam cells formation. Retrospective observations suggest that inhaled corticosteroids may reduce atherothrombotic mortality by attenuating systemic inflammation, but this benefit needs confirmation in ongoing randomized controlled trials. Physicians approaching COPD patients should always be aware of the systemic vascular implications of this disease.
Stereochemical Aspects of the Molecular Pharmaceutics of Ibuprofen

Abstract— Thermal analysis, thermodynamics of solution and molecular modelling of (+)‐ibuprofen and (+)‐ibuprofen gave information on how heterochiral or homochiral interactions would affect the processing of ibuprofen. The study confirmed that (±)‐ibuprofen exists as a true racemate with a 10% eutectic pure enantiomer composition. Both the racemate and the (+)‐isomer crystal unit cells include four molecules and crystallize in the P21/c and P21 space groups, respectively. Thus the intermolecular forces were different in each crystal. As a consequence the (+)‐enantiomer lattice was more fragile but only slightly more soluble than the racemate in aqueous media. The solid‐state structure contributions to solubility were different for the two crystals (ΔH(+) = 51·1 and ΔH(±) = 32–2 kJ mol−1) but the standard free energies of the solutions were comparable for both compounds.
Aspirin Desensitization in Patients With Coronary Artery Disease: Results of the Multicenter ADAPTED Registry (Aspirin Desensitization in Patients With Coronary Artery Disease)

Background— There are limited data on aspirin (ASA) desensitization for patients with coronary artery disease. The aim of the present study was to assess the safety and efficacy of a standard rapid desensitization protocol in patients with ASA sensitivity undergoing coronary angiography. Methods and Results— This is a prospective, multicenter, observational study including 7 Italian centers including patients with a history of ASA sensitivity undergoing coronary angiography with intent to undergo percutaneous coronary intervention. A total of 330 patients with history of ASA sensitivity with known/suspected stable coronary artery disease or presenting with an acute coronary syndrome, including ST-segment–elevation myocardial infarction were enrolled. Adverse effects to aspirin included urticaria (n=177, 53.6%), angioedema (n=69, 20.9%), asthma (n=65, 19.7%), and anaphylactic reaction (n=19, 5.8%). Among patients with urticaria/angioedema, 13 patients (3.9%) had a history of idiopathic chronic urticaria. All patients underwent a rapid ASA (5.5 hours) desensitization procedure. The desensitization procedure was performed before cardiac catheterization in all patients, except for those (n=78, 23.6%) presenting with ST-segment–elevation myocardial infarction who underwent the desensitization after primary percutaneous coronary intervention. Percutaneous coronary intervention was performed in 235 patients (71%) of the overall study population. The desensitization procedure was successful in 315 patients (95.4%) and in all patients with a history of anaphylactic reaction. Among the 15 patients (4.6%) who did not successfully respond to the desensitization protocol, adverse reactions were minor and responded to treatment with corticosteroids and antihistamines. Among patients with successful in-hospital ASA desensitization, 253 patients (80.3%) continued ASA for at least 12 months. Discontinuation of ASA in the 62 patients (19.7%) who had responded to the desensitization protocol was because of medical decision and not because of hypersensitivity reactions. Conclusions— A standard rapid desensitization protocol is safe and effective across a broad spectrum of patients, irrespective of the type of aspirin sensitivity manifestation, with indications to undergo coronary angiography with intent to perform percutaneous coronary intervention. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT02848339.
Cave features, seasonality and subterranean distribution of non-obligate cave dwellers

Seasonality impacts species distributions through changes of the environmental conditions that affect the presence of individuals at a given place. Although the dynamics of cave microclimates are well known, only a few studies have evaluated the effects of such dynamics on non-strictly cave species. Here we assessed if species exploiting subterranean environments show changes in habitat occupation related to seasonal variation of cave microclimates. We surveyed 16 caves in central Italy every month for one year. Caves were subdivided into longitudinal sectors of three meters. In each sector we measured cave morphology and microclimatic features, assessed the occurrence of eight non-troglobitic taxa (orthopterans, spiders, gastropods and amphibians), and related species distribution to environmental features and sampling periods. The occurrence of most species was related to both cave morphology and microclimatic features. The survey month was the major factor determining the presence of species in cave sectors, indicating that cave-dwelling taxa show strong seasonality in activity and distribution. For multiple species, we detected interactions between sampling period and microclimatic features, suggesting that species may associate with different microhabitats throughout the year. The richest communities were found in sites with specific microclimates (i.e., high humidity, warm temperature and low light) but seasonality for species richness was strong as well, stressing the complexity of interactions between outdoor and subterranean environments.
BAL fluid contains detectable superoxide dismutase 1 activity.

OBJECTIVE This study determined which, if any, of the three superoxide dismutase (SOD) enzyme activities were detectable in BAL fluid (BALF). BACKGROUND The identity and concentrations of antioxidant molecules in BALF have not been fully characterized. One important class of antioxidants is that of the SOD enzymes. METHODS BALF from control nonsmokers (n=9), smokers (n=7), and asthmatic subjects (n=12) were examined for SOD activity by a modified pyrogallol auto-oxidation method. The particular SOD enzyme or enzymes responsible for any activity were identified based on activity inhibition data and gel filtration column chromatography patterns. RESULTS SOD activity was detected in all samples. Unlike serum or some other fluids, in which the enzyme extracellular SOD accounts for virtually all SOD activity, the enzyme SOD 1 accounted for virtually all SOD activity. BALF SOD activities were lower for smokers than for control or asthmatic subjects (p<0.05). CONCLUSION BALF SOD 1 activities can be measured as part of lung antioxidant studies. Data from a limited number of subjects suggested that smokers can have low BALF SOD values.
Prevalence of and risk factors for sarcopenia in elderly Chinese men and women.

BACKGROUND Several studies have documented the substantial health and economic burdens associated with sarcopenia among the elderly, but there has been no systematic study among Asians. A cross-sectional survey of elderly community-dwelling Chinese volunteers (262 men and 265 women), aged 70 years and older, was undertaken in Hong Kong. The purposes of this study were to evaluate the prevalence of and risk factors for sarcopenia in elderly Chinese, and to compare these observations with those in white persons. METHODS Muscle mass was estimated by dual-energy X-ray absorptiometry. In this study, sarcopenia was defined as a total adjusted skeletal muscle mass two standard deviations or more below the normal mean for young Asian men and women in this study. The relationship between risk factors (alcohol consumption, cigarette smoking, regular exercise, body mass index, medical conditions) and sarcopenia was studied by multiple logistic regression. RESULTS The prevalence of sarcopenia was 12.3% in Chinese men and 7.6% in Chinese women aged 70 years and older, which was slightly lower than figures observed in white persons. Being underweight was a significant risk factor in both men (odds ratio, 39.1; 95% confidence interval, 11.3 to 134.6) and women (odds ratio, 9.7; 95% confidence interval, 2.8 to 33.8). No other risk factors were found in Chinese men or women. CONCLUSIONS Sarcopenia exists among elderly Chinese men and women, albeit at a lower rate than in white persons. This may be due to the lower muscle mass among young men and women or to an attenuated rate of loss in muscle mass with aging in the Chinese elderly. Being underweight is a major risk factor for sarcopenia in both sexes.
Formation condition of monohydrocalcite

Monohydrocalcite (CaCO 3 H 2 O: MHC) was found from sediment core at lake Hovsgol, Mongolia. It is estimated that MHC was formed during the cold periods. It may be possible to estimate water quality condition of lake Hovsgol during the cold periods by understanding the formation condition of MHC. Synthesis experiments of carbonate minerals from various concentration of Ca, Mg CO 3 were conducted to ﬁnd the formation condition of MHC. MHC was produced when the original solution condition was Ca < CO 3 and Mg existed. Crystal morphology of MHC was observed by scanning electron microscope. The morphology of MHC was spherocrystal that aggregate acicular or long column crystal, and bow-tie-shaped crystal depending on Mg/Ca ra-tio in original solution. In present study, the equilibrium constant of MHC formation reaction was estimated from the reaction solutions.
Experimental sleep deprivation as a tool to test memory deficits in rodents

Paradigms of sleep deprivation (SD) and memory testing in rodents (laboratory rats and mice) are here reviewed. The vast majority of these studies have been aimed at understanding the contribution of sleep to cognition, and in particular to memory. Relatively little attention, instead, has been devoted to SD as a challenge to induce a transient memory impairment, and therefore as a tool to test cognitive enhancers in drug discovery. Studies that have accurately described methodological aspects of the SD protocol are first reviewed, followed by procedures to investigate SD-induced impairment of learning and memory consolidation in order to propose SD protocols that could be employed as cognitive challenge. Thus, a platform of knowledge is provided for laboratory protocols that could be used to assess the efficacy of drugs designed to improve memory performance in rodents, including rodent models of neurodegenerative diseases that cause cognitive deficits, and Alzheimer's disease in particular. Issues in the interpretation of such preclinical data and their predictive value for clinical translation are also discussed.
Current trends in translational research in leptospirosis

Purpose of review In the past years, the importance of studying leptospirosis in a translational context has become more evident. This review addresses recent findings in the study of leptospirosis infection, focusing on those applicable to public health, or that will affect management and diagnosis of cases of leptospirosis. Recent findings We review here recent findings regarding translational aspects of leptospirosis research. Briefly, PCR or a combination of serology and PCR seem to have a higher sensitivity than the current gold standard (microagglutination test). More clinical trials are needed to determine the best treatment for mild and severe leptospirosis. Dendritic cells and &ggr;&dgr; T cells seem to have an important role in the immune response to leptospirosis. Environmental assessment is emerging as a very useful tool. Summary In order to understand leptospirosis, multiple aspects need to be considered, including host, pathogen and environment. In this review, we will address newer diagnostics, current advances in immunology and treatment and the growing role of environmental assessment.
The PREP system of nursing interventions: a pilot test with families caring for older members. Preparedness (PR), enrichment (E) and predictability (P).

The PREP system of nursing interventions, designed to increase preparedness (PR), enrichment (E), and predictability (P) in families providing care to older people, was pilot tested for acceptability and preliminary effectiveness. Eleven family units were assigned to the PREP group and 11 to a standard home health control group. The PREP group scored approximately one SD higher than the control group (p < .05) on the Care Effectiveness Scale, indicating greater preparedness, enrichment, and predictability. Further, on a rating of overall usefulness, the PREP group rated their assistance from PREP nurses (M = 9.75) as significantly higher (p < .01) than the control group rated assistance from the home health nurse or physical therapist (M = 6.57). Although not statistically significant, mean hospital costs for the PREP group ($2,775) were lower than for the control group ($6,929). Results provided support for a full intervention trial.
STEREO OBSERVATIONS OF ENERGETIC NEUTRAL HYDROGEN ATOMS DURING THE 2006 DECEMBER 5 SOLAR FLARE

We report the discovery of energetic neutral hydrogen atoms (ENAs) emitted during the X9 solar event of 2006 December 5. Beginning ∼1 hr following the onset of this E79 flare, the Low Energy Telescopes (LETs) on both the STEREO A and B spacecraft observed a sudden burst of 1.6–15 MeV protons beginning hours before the onset of the main solar energetic particle event at Earth. More than 70% of these particles arrived from a longitude within ±10° of the Sun, consistent with the measurement resolution. The derived emission profile at the Sun had onset and peak times remarkably similar to the GOES soft X-ray profile and continued for more than an hour. The observed arrival directions and energy spectrum argue strongly that the particle events < 5 MeV were due to ENAs. To our knowledge, this is the first reported observation of ENA emission from a solar flare/coronal mass ejection. Possible origins for the production of ENAs in a large solar event are considered. We conclude that the observed ENAs were most likely produced in the high corona and that charge-transfer reactions between accelerated protons and partially stripped coronal ions are an important source of ENAs in solar events.
Mechanical Characteristics of Self-Consolidating Concretes Exposed to Elevated Temperatures

Mechanical characteristics of self-consolidating concretes subjected to elevated temperatures up to 700°C were experimentally investigated in this paper. Eight different concretes [four self-consolidating concretes (SCC) and four conventional concretes (CC)] of different strength categories were produced. At the age of 120 days, specimens were placed in an electrical furnace and the heating was applied at a rate of 5°C∕min until the desired temperature was reached. A maximum temperature of 100, 300, 500, and 700°C was maintained for 1 h . Specimens were then allowed to cool in the furnace and tested for compressive strength, splitting tensile strength, and ultrasonic pulse velocity. Similar tests were also performed at room temperature (20°C) for the reference specimens. Residual strength of both SCC and CC was reduced almost similar up to the maximum temperature tested. Explosive spalling occurred in both SCC and CC of the highest strength category at temperatures greater than 380°C . The residual compre.
Biochemical markers in persons with preclinical familial Alzheimer disease

Background: Persons at risk for familial Alzheimer disease (FAD) provide a model in which biomarkers can be studied in presymptomatic disease. Methods: Twenty-one subjects at risk for presenilin-1 (n = 17) or amyloid precursor protein (n = 4) mutations underwent evaluation with the Clinical Dementia Rating (CDR) scale. We obtained plasma from all subjects and CSF from 11. Plasma (Aβ40, Aβ42, F2-isoprostanes) and CSF (F2-isoprostanes, t-tau, p-tau181, Aβ40, Aβ42, and Aβ42/Aβ40 ratio) levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs). Results: Plasma Aβ42 levels (25.1 pM vs 15.5 pM, p = 0.031) and the ratio of Aβ42/Aβ40 (0.16 vs 0.11, p = 0.045) were higher in presymptomatic MCs. Among MCs, those with CDR scores of 0.5 had lower plasma Aβ42 levels than those with CDR scores of 0 (14.1 pM vs 25.1, p = 0.02). The ratio of Aβ42 to Aβ40 was also reduced in the CSF (0.08 vs 0.15, p = 0.046) of nondemented MCs compared to NCs. Total CSF tau and p-tau181 levels were elevated in presymptomatic FAD MCs. CSF levels of F2-isoprostanes were also elevated in MCs (n = 7, 48.6 pg/mL) compared to NCs (n = 4, 21.6 pg/mL, p = 0.031). Conclusions: Our data indicate that Aβ42 is elevated in plasma in familial Alzheimer disease (FAD) mutation carriers (MCs) and suggests that this level may decrease with disease progression prior to the development of overt dementia. We also demonstrated that the ratio of Aβ42 to Aβ40 was reduced in the CSF of nondemented MCs and that elevations of t-tau and p-tau181 are sensitive indicators of presymptomatic disease. Our finding of elevated F2-isoprostane levels in the CSF of preclinical FAD MCs suggests that oxidative stress occurs downstream to mismetabolism of amyloid precursor protein.