Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of molecules involved in antigen presentation and T cell activation (HLA-DR, CD80, CD86, CD44 and CD54) by cultured human osteoblasts.

BACKGROUND Osteoblasts express the CD44 antigen and HLA class II antigens, molecules which, together with other costimulatory molecules such as CD80, CD86, and CD54, are involved in antigen presentation and T cell activation. The aim of this study was to investigate the expression of these molecules in human osteoblasts. METHODS Human osteoblastic cells obtained from samples of normal bone obtained during mandibular osteotomy were isolated, maintained in culture, and characterized. The identity of the cells was confirmed by their alkaline phosphatase activity and their capacity to produce osteocalcin. Flow cytometry was used to examine the expression HLA-DR, CD80, CD86, CD44, and CD54 molecules involved in immune activities. RESULTS We detected the expression of CD10, CD44, and HLA-DR antigens, molecules involved in antigen presentation in cultured osteoblastic cells. Although the cells were negative for CD45, the leukocyte common antigen and CD14 (an antigen detected on macrophages), they expressed CD54, CD80, and CD86 antigens, which are also involved in the mechanisms of antigen presentation to and activation of T cells. CONCLUSIONS Our results suggest that osteoblastic cells or a subpopulation of these cells may have immune functions in bone. Further studies in which immune functions are assessed will be needed to test this hypothesis.
Carotid body chemoreceptors in dissociated cell culture

Carotid body (CB) glomus or type 1 cells act as peripheral chemoreceptors which detect changes in arterial PO2, PCO2, and pH and help maintain homeostasis via the reflex control of ventilation. Over the last ∼12 years significant progress has been made towards understanding chemotransduction mechanisms using freshly isolated or cultured type 1 cells. The latter preparation allows several powerful experimental manipulations (e.g., co‐culture with sensory neurons) resulting in significant advances in our understanding of CB chemoreception. Here, we review several properties of type 1 cells after several days to weeks in culture. Typically, cultured type 1 cells grow in monolayer clusters enveloped by glial‐like, type II, or sustentacular cells, which are immunopositive for the glial marker, glial fibrillary acid protein (GFAP). These cells can undergo DNA synthesis, evidenced by uptake of bromodeoxyuridine (BrdU), and show a limited capacity for cell division. Mitosis and survival of type 1 cells can be regulated by oxygen tension and/or growth factors (e.g., bFGF, insulin). In the rat, type 1 cells are immunopositive for several monoaminergic markers, including tyrosine hydroxylase (TH), dopamine transporter (DAT), and 5‐HT. They also express cholinergic markers (e.g., vesicular acetylcholine transporter; VAChT), the highly conserved synaptic vesicle protein (SV2), and gap junctional proteins including Connexin 32 (Cx32). Moreover, in long‐term culture (∼2 weeks) they retain expression of O2‐sensitive, TASK‐1‐like, and Ca2+‐dependent (BK), K+ channels as revealed by immunocytochemistry or RT‐PCR analysis of mRNA extracted from type 1 clusters after removal from the culture surface. Microsc. Res. Tech. 59:249–255, 2002. © 2002 Wiley‐Liss, Inc.
Store-Operated Calcium Channel Complex in Postsynaptic Spines: A New Therapeutic Target for Alzheimer's Disease Treatment

Mushroom dendritic spine structures are essential for memory storage and the loss of mushroom spines may explain memory defects in aging and Alzheimer's disease (AD). The stability of mushroom spines depends on stromal interaction molecule 2 (STIM2)-mediated neuronal-store-operated Ca2+ influx (nSOC) pathway, which is compromised in AD mouse models, in aging neurons, and in sporadic AD patients. Here, we demonstrate that the Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 channels form a STIM2-regulated nSOC Ca2+ channel complex in hippocampal mushroom spines. We further demonstrate that a known TRPC6 activator, hyperforin, and a novel nSOC positive modulator, NSN21778 (NSN), can stimulate activity of nSOC pathway in the spines and rescue mushroom spine loss in both presenilin and APP knock-in mouse models of AD. We further show that NSN rescues hippocampal long-term potentiation impairment in APP knock-in mouse model. We conclude that the STIM2-regulated TRPC6/Orai2 nSOC channel complex in dendritic mushroom spines is a new therapeutic target for the treatment of memory loss in aging and AD and that NSN is a potential candidate molecule for therapeutic intervention in brain aging and AD. SIGNIFICANCE STATEMENT Mushroom dendritic spine structures are essential for memory storage and the loss of mushroom spines may explain memory defects in Alzheimer's disease (AD). This study demonstrated that Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 form stromal interaction molecule 2 (STIM2)-regulated neuronal-store-operated Ca2+ influx (nSOC) channel complex in hippocampal synapse and the resulting Ca2+ influx is critical for long-term maintenance of mushroom spines in hippocampal neurons. A novel nSOC-positive modulator, NSN21778 (NSN), rescues mushroom spine loss and synaptic plasticity impairment in AD mice models. The TRPC6/Orai2 nSOC channel complex is a new therapeutic target and NSN is a potential candidate molecule for therapeutic intervention in brain aging and AD.
Sterol transfer by atypical cholesterol-binding NPC2 proteins in coral-algal symbiosis

Reef-building corals depend on intracellular dinoflagellate symbionts that provide nutrients. Besides sugars, the transfer of sterols is essential for corals and other sterol-auxotrophic cnidarians. Sterols are important cell components, and variants of the conserved Niemann-Pick Type C2 (NPC2) sterol transporter are vastly up-regulated in symbiotic cnidarians. Types and proportions of transferred sterols and the mechanism of their transfer, however, remain unknown. Using different pairings of symbiont strains with lines of Aiptasia anemones or Acropora corals, we observe both symbiont- and host-driven patterns of sterol transfer, revealing plasticity of sterol use and functional substitution. We propose that sterol transfer is mediated by the symbiosis-specific, non-canonical NPC2 proteins, which gradually accumulate in the symbiosome. Our data suggest that non-canonical NPCs are adapted to the symbiosome environment, including low pH, and play an important role in allowing corals to dominate nutrient-poor shallow tropical seas worldwide.
The effect of a physiological increase in temperature on mitochondrial fatty acid oxidation in rat myofibres.

We investigated the effect of temperature increase on mitochondrial fatty acid (FA) and carbohydrate oxidation in the slow-oxidative skeletal muscles (soleus) of rats. We measured mitochondrial respiration at 35 and 40°C with the physiological substrates pyruvate + 4mM malate (Pyr) and palmitoyl-CoA + 0.5mM malate + 2mM carnitine (PCoA) in permeabilised myofibres under non-phosphorylating ( 0) or phosphorylating ( max) conditions. Mitochondrial efficiency was calculated by the respiratory control ratio (RCR = max/ 0). We used guanosine triphosphate (GTP), an inhibitor of uncoupling protein (UCP), to study the mechanisms responsible for alterations of mitochondrial efficiency. We measured hydrogen peroxide (H2O2) production under non-phosphorylating and phosphorylating conditions at both temperatures and substrates. We studied citrate synthase (CS) and 3-hydroxyl acyl coenzyme A dehydrogenase (3-HAD) activities at both temperatures. Elevating the temperature from 35 to 40°C increased PCoA- 0 and decreased PCoA-RCR, corresponding to the uncoupling of oxidative phosphorylation (OXPHOS). GTP blocked the heat-induced increase of PCoA- 0. Rising temperature moved towards a Pyr- 0 increase, without significance. Heat did not alter H2O2 production resulting from either PCoA or Pyr oxidation. Heat induced an increase in 3-HAD but not in CS activities. In conclusion, heat induced OXPHOS uncoupling for PCoA oxidation which was, at least partially, mediated by UCP and independent of oxidative stress. The classically described heat-induced glucose shift may actually be mostly due to a less efficient FA oxidation. These findings raise questions concerning the consequences of heat-induced alterations in mitochondrial efficiency of FA metabolism on thermoregulation.
Plasma copper and the risk of first stroke in hypertensive patients: a nested case-control study.

BACKGROUND Previous studies indicated that trace elements may play an important role in cardiovascular diseases. However, data concerning the association between blood copper and the risk of stroke are limited. OBJECTIVE The aim of this study was to evaluate the association between plasma copper and the risk of first stroke, and examine any possible effect modifiers in hypertensive patients. METHODS We conducted a nested case-control study, using data from the China Stroke Primary Prevention Trial. Hypertension is defined as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or taking antihypertensive medication. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. The crude and adjusted risks of first stroke were estimated by ORs and 95% CIs using conditional logistic regression, without or with adjusting for pertinent covariates, respectively. RESULTS There were significant positive associations of plasma copper with risk of first stroke (per SD increment-OR: 1.20; 95% CI: 1.03, 1.39) and first ischemic stroke (OR: 1.26; 95% CI: 1.07, 1.50). When plasma copper was categorized in quartiles, significantly higher risks of first stroke (OR: 1.72; 95% CI: 1.12, 2.65) and first ischemic stroke (OR: 1.91; 95% CI: 1.18, 3.11) were found in participants in quartile 4 (≥ 117.0 μg/dL) than in those in quartile 1 (< 91.2 μg/dL). Furthermore, the plasma copper-first stroke association was significantly stronger in participants with higher BMI (< 25.0 compared with ≥ 25.0 kg/m2, P-interaction = 0.024). However, there was no significant association between plasma copper and first hemorrhagic stroke. CONCLUSIONS In Chinese hypertensive patients, there was a significant positive association between baseline plasma copper and the risk of first stroke, especially among those with higher BMI.This trial was registered at clinicaltrials.gov as NCT00794885.
Studies on the subthalamus of the rhesus monkey. II. Hyperkinesia and other physiologic effects of subthalamic lesions, with special reference to the subthalamic nucleus of Luys

I . Introduction . I1 . Observations . Hyperkinesia . Choreoid hyperkinesia . Illustrative protocols . Characteristics of choreoid hyperkinesia provoked by subthalamic lesions . Characteristics of lesions provoking choreoid hyperkinesia . Analysis of integrity of adjacent structures . Choreoid hyperkinesia associated with lesions in connections of subthalamicnucleus . Surgical analysis of subthalamic choreoid hyperkinesia . Pharmacological analysis of choreoid hyperkinesia . Choreoid hyperkinesia with intact subthalamic nucleus . Tremor . Protocol . Other abnormalities . Hypokinesia . Paresis . Spasticity . Ocular abnormalities . Temperatures . Weights . I11 . Discussion . IV . Summary and conclusions . Acknowledgment . Literature cited . 320 320 320 321 321
Effects of a novel corn-expressed E. coli phytase on digestibility of calcium and phosphorous, growth performance, and bone ash in young growing pigs.

Two experiments were conducted to test the hypothesis that a corn-expressed phytase (GraINzyme, Agrivida, Woburn, MA) increases growth performance, bone measurements, and nutrient digestibility by young growing pigs, if added to diets that are deficient in Ca and P. In Exp. 1, 60 pigs (initial BW: 10.78 ± 0.67 kg) were randomly allotted to 6 dietary treatments that included a positive control diet (PC; 0.70% total Ca and 0.60% total P) and a negative control diet (NC; 0.50% total Ca and 0.42% total P). Four additional diets were formulated by supplementing the NC diet with 250, 500, 1,000, or 1,500 phytase units (FTU)/kg. Diets were fed for 28 d and the individual BW of pigs on d 1 and d 28 were recorded. Fecal samples were collected from d 25 to 27 to calculate apparent total tract digestibility (ATTD) of Ca and P. On the last d of the experiment, all pigs were euthanized and the left femur was removed and analyzed for ash, Ca, and P. Results indicated that growth performance, ATTD of Ca and P, and bone ash measurements were reduced (P < 0.05) in NC fed pigs compared with PC fed pigs. However, growth performance, ATTD of Ca and P, and bone ash measurements were improved (linear and quadratic, P < 0.05) by including increasing concentrations of phytase to the NC diet. In Exp. 2, experimental procedures were similar to those used in Exp. 1. Forty-eight pigs (initial BW: 11.15 ± 0.85 kg) were randomly allotted to 6 dietary treatments in a 28 d experiment. Treatments included a PC diet, a NC diet, and 4 diets in which 500 or 1,000 FTU/kg of either the corn-expressed phytase or a commercial microbial phytase (AxtraPhy, Danisco Animal Nutrition-DuPont Industrial Biosciences, Waukesha, WI) were added to the NC diet. Pigs fed the NC diet had reduced (P < 0.01) final BW, ADG, G:F, and bone ash concentrations compared with pigs fed the PC diet. When 500 FTU/kg phytase was fed, no differences were observed in growth performance or bone ash measurements between phytase sources, and there were no differences in growth performance among pigs fed 1,000 FTU/kg of either phytase source and the PC diet. However, regardless of concentration or source of phytase, pigs fed the PC diet had greater (P < 0.001) amount of bone ash, bone Ca, and bone P compared with pigs fed phytase diets. In conclusion, the corn-expressed phytase is effective in improving growth performance, Ca and P digestibility, and bone measurements in pigs fed diets that are deficient in Ca and P.
Emergent decision-making behaviour and rhythm generation in a computational model of the ventromedial nucleus of the hypothalamus

The ventromedial nucleus of the hypothalamus (VMN) has an important role in diverse behaviours. The common involvement in these of sex steroids, nutritionally-related signals, and emotional inputs from other brain areas, suggests that, at any given time, its output is in one of a discrete number of possible states corresponding to discrete motivational drives. Here we explored how networks of VMN neurons might generate such a decision-making architecture. We began with minimalist assumptions about the intrinsic properties of VMN neurons inferred from electrophysiological recordings of these neurons in rats in vivo, using an integrate-and-fire based model modified to simulate activity-dependent post-spike changes in neuronal excitability. We used a genetic algorithm based method to fit model parameters to the statistical features of spike patterning in each cell. The spike patterns in both recorded cells and model cells were assessed by analysis of interspike interval distributions and of the index of dispersion of firing rate over different binwidths. Simpler patterned cells could be closely matched by single neuron models incorporating a hyperpolarising afterpotential and either a slow afterhyperpolarisation or a depolarising afterpotential, but many others could not. We then constructed network models with the challenge of explaining the more complex patterns. We assumed that neurons of a given type (with heterogeneity introduced by independently random patterns of external input) were mutually interconnected at random by excitatory synaptic connections (with a variable delay and a random chance of failure). Simple network models of one or two cell types were able to explain the more complex patterns. We then explored the information processing features of such networks that might be relevant for a decision-making network. We concluded that rhythm generation (in the slow theta range) and bistability arise as emergent properties of networks of heterogeneous VMN neurons.
Comparison of the ligand‐binding properties of fluorescent VEGF‐A isoforms to VEGF receptor 2 in living cells and membrane preparations using NanoBRET

Vascular endothelial growth factor A (VEGF‐A) is a key mediator of angiogenesis. A striking feature of the binding of a fluorescent analogue of VEGF165a to nanoluciferase‐tagged VEGF receptor 2 (VEGFR2) in living cells is that the BRET signal is not sustained and declines over time. This may be secondary to receptor internalisation. Here, we have compared the binding of three fluorescent VEGF‐A isoforms to VEGFR2 in cells and isolated membrane preparations.
Accountability Assessment of Health Improvements in the United States Associated with Reduced Coal Emissions Between 2005 and 2012.

BACKGROUND National, state, and local policies contributed to a 65% reduction in sulfur dioxide emissions from coal-fired power plants between 2005 and 2012 in the United States, providing an opportunity to directly quantify public health benefits attributable to these reductions under an air pollution accountability framework. METHODS We estimate ZIP code-level changes in two different-but related-exposure metrics: total PM2.5 concentrations and exposure to coal-fired power plant emissions. We associate changes in 10 health outcome rates among approximately 30 million US Medicare beneficiaries with exposure changes between 2005 and 2012 using two difference-in-difference regression approaches designed to mitigate observed and unobserved confounding. RESULTS Rates per 10,000 person-years of six cardiac and respiratory health outcomes-all cardiovascular disease, chronic obstructive pulmonary disorder, cardiovascular stroke, heart failure, ischemic heart disease, and respiratory tract infections-decreased by between 7.89 and 1.95 per (Equation is included in full-text article.)decrease in PM2.5, with comparable decreases in coal exposure leading to slightly larger rate decreases. Results for acute myocardial infarction, heart rhythm disorders, and peripheral vascular disease were near zero and/or mixed between the various exposure metrics and analyses. A secondary analysis found that nonlinearities in relationships between changing health outcome rates and coal exposure may explain differences in their associations. CONCLUSIONS The direct analyses of emissions reductions estimate substantial health benefits via coal power plant emission and PM2.5 concentration reductions. Differing responses associated with changes in the two exposure metrics underscore the importance of isolating source-specific impacts from those due to total PM2.5 exposure.
Screening Criteria for Detecting Severe Ocular Injuries in the Setting of Orbital Fractures.

PURPOSE Define incidence of severe ocular trauma in orbital fracture patients and determine if ocular signs and symptoms are useful predictors of severe ocular injuries. METHODS Retrospective chart review was performed on all patients with orbital fractures between April 1, 2013, and December 31, 2014. Patients were included if they had radiographic evidence of acute fracture of at least one orbital wall and were evaluated by the Ophthalmology service. Demographics, concurrent injury data, and symptoms and signs of ocular trauma were collected. Concurrent ocular injuries were grouped by severity. Predictive signs or symptoms for severe ocular trauma were identified by stepwise logistic regression analysis. The threshold point for predictive signs and symptoms was detected by a receiver operating characteristic (ROC). RESULTS Five-hundred-twelve patients were included. The most common mechanisms of injury were assault (39%), fall (25%), and motor vehicle accident (21%). The incidence of any concurrent ocular trauma was 75% (383/512), with 14% (70/512) being severe. Four signs and symptoms were predictors of severity: blurred vision (P < 0.0001), pain with eye movements (P < 0.0001), visual acuity worse than 20/40 in the ipsilateral eye (P < 0.001), and restricted motility (P < 0.001). The presence of 2 or more of these signs or symptoms was predictive of severe ocular trauma with high sensitivity (91%) and specificity (86%). CONCLUSIONS In cooperative patients with acute orbital wall fractures, the presence of 2 or more signs or symptoms is predictive of severe ocular trauma and necessitates the need for urgent ophthalmic consultation.
Looking beyond PGC-1α: Emerging regulators of exercise-induced skeletal muscle mitochondrial biogenesis and their activation by dietary compounds.

Despite its widespread acceptance as the "master regulator" of mitochondrial biogenesis (i.e. the expansion of the mitochondrial reticulum), peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1 alpha (PGC-1α) appears to be dispensable for the training-induced augmentation of skeletal muscle mitochondrial content and respiratory function. In fact, a number of regulatory protein have emerged as important players in skeletal muscle mitochondrial biogenesis and many of these protein share key attributes with PGC-1α. In an effort to move past the simplistic notion of a "master regulator" of mitochondrial biogenesis, we highlight the regulatory mechanisms by which nuclear factor erythroid 2-related factor 2 (Nrf2), estrogen-related receptor gamma (ERRγ), PPARβ and leucine-rich pentatricopeptide repeat-containing protein (LRP130) may contribute to the control of skeletal muscle mitochondrial biogenesis. We also present evidence supporting/refuting the ability of sulforaphane, quercetin, and epicatechin to promote skeletal muscle mitochondrial biogenesis and their potential to augment mitochondrial training adaptations. Targeted activation of specific pathways by these compounds may allow for greater mechanistic insight into the molecular pathways controlling mitochondrial biogenesis in human skeletal muscle. Dietary activation of mitochondrial biogenesis may also be useful in clinical populations with basal reductions in mitochondrial protein content, enzyme activities, and/or respiratory function as well as individuals who exhibit a blunted skeletal muscle responsiveness to contractile activity. Key points: -The existence of redundant pathways leading to mitochondrial biogenesis refutes the simplistic notion of a "master regulator" of mitochondrial biogenesis. -Dietary activation of specific pathways may provide greater mechanistic insight into the exercise-induced mitochondrial biogenesis in human skeletal muscle.