Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of fatty-acid amide hydrolyse (FAAH) exerts cognitive improvements in male but not female rats.

OBJECTIVES The endocannabinoid system is implicated in the regulation of various brain functions including cognition, memory, and behavior. It has been shown that inhibition of the endocannabinoid-degrading enzyme fatty acid amid hydrolase (FAAH) enhances the memory and learning in males. Given the fact that sexual dimorphism exists in the different components of the endocannabinoid system, the aim of this study was to test the hypothesis that cognition enhancing effect of the acute inhibition of FAAH by URB597 is gender dependent. METHODS In the study, 32 adult male and female Sprague-Dawley rats were used. They were treated with a single intraperitoneal injection of FAAH inhibitor URB597 (0.3 mg/kg) or vehicle 40 min before behavioral testing. The novel object recognition test was used as a working memory task to assess cognitive performance. RESULTS Neither the treatment nor the gender significantly affected the velocity, the total distance travelled and the time spent exploring the familiar object. The recognition of the object was influenced by both URB597 and gender. Male rats treated with URB597 displayed significantly increased novel object exploration compared to males treated with vehicle as well as to female rats treated with URB597. Single administration of URB597 significantly enhanced the recognition index in male, but not female rats. CONCLUSIONS The results demonstrate that the positive effects of FAAH inhibition on the cognition are gender dependent. It is likely that male rats are more vulnerable to the modulation of the endocannabinoid system than female rats.
GPCR-induced dissociation of G-protein subunits in early stage signal transduction

G-protein coupled receptors (GPCRs) form a ternary complex of agonist, receptor and G-proteins during primary signal transduction at the cell membrane. Downstream signalling is thought to be preceded by the process of dissociation of Gα and Gβγ subunits, thus exposing new surfaces to interact with downstream effectors. We demonstrate here for the first time, the dissociation of heterotrimeric G-protein subunits (i.e., Gα and Gβγ) following agonist-induced GPCR (α2A-adrenergic receptor; α2A-AR) activation in a cell-free assay system. α2A-AR membranes were reconstituted with the G-proteins (±hexahistidine-tagged) Gαi1 and Gβ1γ2 and functional signalling was determined following activation of the reconstituted receptor:G-protein complex with the potent agonist UK-14304, and [35S]GTPγS. In the presence of Ni2+-coated agarose beads, the activated his-tagged Gαi1his-[35S]GTPγS complex was captured on the Ni2+-presenting surface. When his-tagged Gβ1γ2 (Gβ1γ2his) was used with Gαi1, the [35S]GTPγS-bound Gαi1 was not present on the Ni2+-coated beads, but rather, it was separated from the β1γ2(his)-beads, demonstrating receptor-induced dissociation of Gα and Gβγ subunits. Treatment of the reconstituted α2A-AR membranes containing Gβ1γ2his:Gαi1 with imidazole confirmed the specificity for the Ni2+:G-protein surface dissociation of Gαi1 from Gβ1γ2his. These data demonstrate for the first time, the complete dissociation of the G-protein subunits and extend observations on the role of G-proteins in the assembly and disassembly of the ternary complex in the primary events of GPCR signalling.
Alpha4beta2 nicotinic receptor status in Alzheimer's disease using 123I-5IA-85380 single-photon-emission computed tomography.

BACKGROUND Loss of the alpha4beta2 nicotinic receptor subtype is found at autopsy in Alzheimer's disease. OBJECTIVE To investigate in vivo changes in this receptor using single-photon-emission CT (SPECT) with 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380), a novel nicotinic acetylcholine receptor ligand which binds predominantly to the alpha4beta2 receptor. METHODS 32 non-smoking subjects (16 with Alzheimer's disease and 16 normal elderly controls) underwent 123I-5IA-85380 and perfusion (99mTc-hexamethylenepropyleneamine oxime (HMPAO)) SPECT scanning. Region of interest analysis was performed with cerebellar normalisation. RESULTS Significant bilateral reductions in nicotinic receptor binding were identified in frontal (left, p = 0.004; right, p = 0.002), striatal (left, p = 0.004; right, p = 0.003), right medial temporal (p = 0.04) and pons (p<0.001) in patients with AD compared to controls. There were no significant correlations with clinical or cognitive measures. The pattern of nicotinic binding significantly differed from that of perfusion in both patients with AD and controls. Both 123I-5IA-85380 and 99mTc-HMPAO SPECT imaging demonstrated similar diagnostic performance in correctly classifying controls and patients with AD. CONCLUSION Using 123I-5IA-85380 SPECT we found changes consistent with significant reductions in the nicotinic alpha4beta2 receptor in cortical and striatal brain regions. This method could facilitate diagnosis and may be useful for monitoring progression of the disease and response to treatment in patients with AD and related diseases.
Skeletal Accelerations Measured during Different Exercises

Exercise is often suggested as a means of reducing the effects of osteoporosis in post-menopausal women. In response to an increase in physical activity, bone mass can be increased and several studies have investigated the effectiveness of different exercises in increasing bone mass. In this study we have attempted to quantify the effect of different exercises by measuring the accelerations produced during various exercises. Accelerations have been measured at the ankle of normal subjects during a series of impulsive (walking, running and walking up and down stairs) and non-impulsive (cycling) exercises. Accelerations were measured using an accelerometer attached to a stiff cuff which straps around the ankle. Signals from the accelerometer are amplified and recorded using a specially developed portable data-logging system. The principal parameters measured were the maximum change of acceleration (peak to peak) and the rate of change of acceleration. From the results it was observed that running and walking up and down stairs produced the highest peak-to-peak change (running = 8.08 g; walking downstairs = 8.11 g) and rate of change of acceleration (running = 2.14 g/s; walking downstairs = 2.07 g/s). By contrast, a non-impulsive exercise such as cycling produced relatively low values of peak-to-peak change (2.24 g) and rate of change (0.23 g/s) of acceleration.
Octenylsuccinic Aciduria in Children Fed Protein-Hydrolysate Formulas Containing Modified Cornstarch

ABSTRACT: The excretion of 2-(2‘-octenyl)succinic acid (OSA) and several metabolites of OSA was studied by gas chromatography/mass spectrometry in 17 infants and children fed one of three proprietary elemental or protein-hydrolysate formulas that use OSA-modified cornstarch as an emulsifying agent. Variable but often large amounts (up to 2500 mg/g creatinine) of the fatty acid-like OSA and its metabolites were found in the urine of these children, and levels of OSA in their blood ranged from 9.5 to 57.9 μmol/L. Apparently secondary abnormalities, such as increased urinary levels of glutaric acid and 2-ketoglutaric acid, were also found in more than half of the urine specimens. The molecular weight and mass fragmentation patterns of the nine compounds associated with the excretion of OSA are consistent with the proposal that OSA is metabolized in human infants and children by a combination of ω-, ω-1-, and β-oxidation steps, similar to the metabolism of another branched-chain fatty acid, valproic acid. The urinary organic acid pattern of children fed elemental formulas containing OSA-modified starch often was dominated by OSA and its metabolites, and in several children the OSA-related changes were mistaken for a primary metabolic disease. Physicians and laboratories evaluating children for suspected metabolic diseases should be aware of the possibility of abnormal organic acid studies associated with OSA-containing formulas. (Pediatr Res 30:564–569, 1991)
Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion

Increasing evidence suggests that mechanical cues inherent to the extracellular matrix (ECM) may be equally as critical as its chemical identity in regulating cell behavior. We hypothesized that the mechanical properties of the ECM directly regulate the motility of vascular smooth muscle cells (SMCs) and tested this hypothesis using polyacrylamide substrates with tunable mechanical properties. Quantification of the migration speed on uniformly compliant hydrogels spanning a range of stiffnesses (Young's moduli values from 1.0 to 308 kPa for acrylamide/bisacrylamide ratios between 5/0.1% and 15/1.2%, respectively) revealed a biphasic dependence on substrate compliance, suggesting the existence of an optimal substrate stiffness capable of supporting maximal migration. The value of this optimal stiffness shifted depending on the concentration of ECM protein covalently attached to the substrate. Specifically, on substrates presenting a theoretical density of 0.8 μg/cm2 fibronectin, the maximum speed of 0.74 ± 0.09 μm/min was achieved on a 51.9 kPa gel; on substrates presenting a theoretical density of 8.0 μg/cm2 fibronectin, the maximum speed of 0.72 ± 0.06 μm/min occurred on a softer 21.6 kPa gel. Pre‐treatment of cells with Y27632, an inhibitor of the Rho/Rho‐kinase (ROCK) pathway, reduced these observed maxima to values comparable to those on non‐optimal stiffnesses. In parallel, quantification of TritonX‐insoluble vinculin via Western blotting, coupled with qualitative fluorescent microscopy, revealed that the formation of focal adhesions and actin stress fibers also depends on ECM stiffness. Combined, these data suggest that the mechanical properties of the underlying ECM regulate Rho‐mediated contractility in SMCs by disrupting a presumptive cell‐ECM force balance, which in turn regulates cytoskeletal assembly and ultimately, cell migration. © 2005 Wiley‐Liss, Inc.
Resurfacing with chemically modified hyaluronic acid and lubricin for flexor tendon reconstruction

We assessed surface coating with carbodiimide derivatized hyaluronic acid combined with lubricin (cd‐HA‐Lubricin) as a way to improve extrasynovial tendon surface quality and, consequently, the functional results in flexor tendon reconstruction, using a canine in vivo model. The second and fifth flexor digitorum profundus tendons from 14 dogs were reconstructed with autologs peroneus longus (PL) tendons 6 weeks after a failed primary repair. One digit was treated with cd‐HA‐Lubricin, and the other was treated with saline as the control. Six weeks following grafting, the digits and graft tendons were functionally and histologically evaluated. Adhesion score, normalized work of flexion, graft friction in zone II, and adhesion breaking strength at the proximal repair site in zone III were all lower in the cd‐HA‐Lubricin treated group compared to the control group. The strength at the distal tendon/bone interface was decreased in the cd‐HA‐Lubricin treated grafts compared to the control grafts. Histology showed inferior healing in the cd‐HA‐Lubricin group at both proximal and distal repair sites. However, cd‐HA‐Lubricin treatment did not result in any gap or rupture at either the proximal or distal repair sites. These results demonstrate that cd‐HA‐Lubricin can eliminate graft adhesions and improve digit function, but that treatment may have an adverse effect on tendon healing. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 969–975, 2013
Aclarubicin‐loaded cationic albumin‐conjugated pegylated nanoparticle for glioma chemotherapy in rats

Traditional glioma chemotherapy with those second‐line drugs such as anthracyclines usually failed because they are inaccessible to blood–brain barrier (BBB) in tumor. In our study, we incorporated aclarubicin (ACL) into cationic albumin‐conjugated pegylated nanoparticle (CBSA‐NP–ACL) to determine its therapeutic potential of rats with intracranially implanted C6 glioma cells. When labeled with fluorescent probe, 6‐coumarin, CBSA‐NP was shown to accumulate much more in tumor mass than nanoparticle without conjugated CBSA (NP) 1 hr post intravenous injection, as well as better retention after 24 hr. Tumor drug concentration of CBSA‐NP–ACL displayed 2.6‐ and 3.3‐fold higher than that of NP–ACL and ACL solution 1 hr post injection, while 2.7 and 6.6‐fold higher after 24 hr, respectively. Moreover, using tumor microdialysis sampling, AUC0–24 hr of free drug amount in tumor interstitium delivered by CBSA‐NP–ACL was about 2.0‐ and 2.7‐fold higher than that of NP–ACL and ACL solutions, respectively. When the tumor rat model was subjected to 4 cycles of 2 mg/kg of ACL in different formulations, a significant increase of median survival time was found in the group of CBSA‐NP–ACL compared with that of saline control animals, animals treated with NP–ACL and ACL solution. By terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end‐labeling, CBSA‐NP–ACL can extensively make the tumor cell apoptosis. Histochemical evaluation by periodic acid Shiff staining and biochemical analysis depicted that the incorporation of ACL into CBSA‐NP reduced its toxicity to liver, kidney and heart. Besides, CBSA‐NP–ACL was not shown to open tight junction evaluated by BBB coculture. It was concluded that CBSA‐NP–ACL could have a therapeutic potential for treatment of glioma. © 2006 Wiley‐Liss, Inc.
The Effects of Selenium Supplementation on Glucose Metabolism and Lipid Profiles Among Patients with Metabolic Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of selenium administration on glucose metabolism and lipid profiles among patients with diseases related to metabolic syndrome (MetS). We searched the following databases up to May 2017: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and assessed for quality of the studies according to the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as standardized mean difference (MDs) with 95% confidence intervals (95% CI). Five studies were included in the meta-analyses. The results showed that selenium supplementation significantly reduced insulin levels (SMD −0.42; 95% CI, −0.83 to −0.01) and increased quantitative insulin sensitivity check index (QUICKI) (SMD 0.83; 95% CI, 0.58 to 1.09). Selenium supplementation had no beneficial effects on other glucose homeostasis parameters, such as fasting plasma glucose (FPG) (SMD −0.29; 95% CI, −0.73 to 0.15), homeostasis model assessment of insulin resistance (HOMA-IR) (SMD −0.80; 95% CI, −1.58 to −0.03), and lipid profiles, such as triglycerides (SMD −0.42; 95% CI, −0.83 to −0.01), VLDL- (SMD −0.42; 95% CI, −0.83 to −0.01), total- (SMD −0.42; 95% CI, −0.83 to −0.01), LDL- (SMD 0.02; 95% CI, −0.20 to 0.24), and HDL-cholesterol (SMD 0.16; 95% CI, −0.06 to −0.38). Overall, this meta-analysis showed that selenium administration may lead to an improvement in insulin and QUICKI, but did not affect FPG, HOMA-IR, and lipid profiles.
Effects of cell culture time and bone matrix exposure on calmodulin content and ATP dependent cell membrane acid transport in avian osteoclasts and macrophages

Osteoclasts mediate bone resorption by secretion at the site of bone attachment. This process depends on calmodulin concentrated at a specialized acid‐secreting membrane. We hypothesized that increased calmodulin and bone attachment were required for acid secretion. We tested this by studying calmodulin, bone attachment, and membrane acid transport in osteoclasts and their precursor mononuclear cells. Osteoclasts and macrophages were isolated from medullary bone of hens; cell fractions were prepared after culturing cells with or without bone. Calmodulin was visualized by Western analysis; calmodulin mRNA was determined by Northern hybridization, and ATP‐dependent membrane acid transport was assayed by acridine orange uptake. Calmodulin decreased in osteoclasts cultured without bone. Calmodulin in isolated macrophages was ∼︁25% of osteoclast levels, but increased several fold by 5 days. Bone had no effect. Calmodulin mRNA was similar in osteoclasts with or without bone. However, only osteoclasts cultured with bone retained acid transport capacity. Macrophage calmodulin mRNA was not affected by bone, but increased three fold by day 5, paralleling protein production. Macrophages developed acid transport capacity at 3–5 days, but at lower levels than osteoclasts, and bone had no measurable effect. Chicken cells express 1.6 kb and inducible 1.9 kb calmodulin transcripts; in macrophages and osteoclasts, the 1.9 kb transcript predominated. We conclude that, following isolation, calmodulin levels decline in osteoclasts via a post‐transcriptional mechanism. In cultured macrophages, by contrast, calmodulin mRNA, protein, and acid secretion increase with time independently of bone substrate, possibly reflecting differentiation in vitro. Increased calmodulin correlated with membrane acid transport capacity in both cell types. The macrophage findings indicate that stimuli other than bone influence acid transport capacity in this family of cells. © 1996 Wiley‐Liss, Inc.
Quantitative contribution of the collagen network in dentin hybridization.

PURPOSE To determine the quantitative contribution of dentin hybridization to bonded assembly strength and demonstrate the micromorphology of the interface with and without collagen present. MATERIALS AND METHODS Four groups of 10 molar teeth were finished to a 320 grit dentin smear layer. Two groups served as controls and two experimental groups were subjected to collagenase digestion of the collagen exposed by acid conditioning. All-Bond 2 and Amalgambond were used to bond Bisfil and Epic resin composite, respectively. Stored in water at 37 degrees C for 24 hours the assemblies were tested in a shear mode at a crosshead speed of 5 mm/minute. Means and standard deviations were subjected to analysis for statistical significance. Twenty four teeth in four groups were examined by scanning (SEM) and transmission electron microscopy (TEM) for the relationship between resin and conditioned dentin with and without the collagen network. RESULTS All-Bond 2 and Amalgambond controls were 28.41 +/- 3.9 and 19.04 +/- 5.96 MPa, collagenase-treated groups scored 26.43 +/- 2.90 and 19.70 +/- 4.25 MPa respectively. No significant difference existed between the control and experimental groups. SEM showed an intertubular collagen network with patent tubules and a pronounced porous, irregular dentin topography following collagen digestion. A distinct hybrid zone and tubular penetration was observed but the collagenase-treated specimens showed only resin in the tubules and their lateral extensions. TEM confirmed the absence of a distinct hybrid zone in the collagenase groups with a tight, gap-free junction between the resin and the undemineralized dentin. An electron dense zone (< 50 nm) at the leading edge of conditioning was observed for All-Bond 2 and Amalgambond groups. It was concluded that the resin-reinforced or hybridized, collagenous network does not detract from, nor contribute any significant quantitative value per se to dentin bonding with the systems tested.
A Prefiltering C-RAN Architecture with Compressed Link Data Rate in Massive MIMO

Massive multiple-input multiple-output (MIMO) is a promising technology in the next 5G communications. Directly merging massive MIMO with cloud radio access network (C-RAN) systems will cause disastrous link data overload, which greatly exceeds the limitation of current 4G wireless standards. To solve this problem, we propose a pre-filtering C-RAN architecture in this paper to compress the inter connection link data rate between remote radio units (RRUs) and baseband units (BBUs), which is based on the structure of linear data detection algorithms and able to achieve lossless performance if perfect channel information (CSI) can be acquired. To make the pre-filtering architecture feasible in practical environments, we further propose two channel estimation methods. One using demodulation reference signal (DMRS) can achieve the data rate compression without performance loss, while the other using sounding reference signal (SRS) can keep the thin structures of RRUs as much as possible. Analysis on practical systems and simulation results show that the proposed architecture can provide a better trade off between hardware implementation cost, system performance and traffic load reduction than conventional architectures.
Neurodevelopmental outcome of young pediatric intensive care survivors of serious brain injury*

Objectives To determine the number of children with severe brain injury due to closed head injury or hypoxic-ischemic encephalopathy as a proportion of all admissions of children <3 yrs of age in the regional pediatric intensive care unit; to determine the outcome of these children at >6 mos postinjury; and to explore the relationship of outcome measures to predictors of outcome obtained within the first 24 hrs after brain injury. Design Prospective, descriptive outcome study of an inception cohort. Results Neonatal and Infant Follow-up Clinic, Glenrose Rehabilitation Hospital, Edmonton, Canada. Patients Of a cohort of 53 children of <3 yrs of age (4% of pediatric intensive care unit admissions, 1995–1998) admitted for severe acquired brain injury (Glasgow Coma Score, ≤8), 12 (23%) died, three (6%) were lost to follow-up, and 38 (71%) survived and received multidisciplinary outcome assessments. Measurements and Main Results Of 50 children with known outcome, 23 (46%) had a good recovery on the Glasgow Outcome Scale; however, only eight (16%) of these had average or above scores on both the mental and motor developmental indices of the Bayley Scales of Infant Development-II at 18–36 mos of age. Acute injury predictors of adverse outcome were apnea at scene, bolus epinephrine given for resuscitation, pupils nonreactive, arterial pH ≤7.2, and Glasgow Coma Score of 3. For 38 survivors, sensitivity and specificity from predictors for the Glasgow Outcome Scale were 73% and 83% respectively; for mental scores, 86% and 93%; for motor scores, 75% and 89%. Conclusions Of children of <3 yrs of age identified by a Glasgow Coma Score of ≤8 after acute brain injury, >80% have adverse outcome of death, disability, or mental or motor developmental scores below average. A Glasgow Outcome Scale of 5 overestimates good recovery. Universal registry and follow-up of these children are needed.