Miracle-dz/UniFAR-FTUs huggingface dataset:
Peripheral gastric leptin modulates brain stem neuronal activity in neonates.

Afferent sensory fibers are the primary neuroanatomic link between nutrient-related events in the gastrointestinal tract and the central neural substrates that modulate ingestion. In this study, we evaluated the peripheral gastric effects of leptin (OB protein) on brain stem neuronal activities using an in vitro neonatal rat preparation. We also tested gastric leptin effects as a function of age in neonates. For ∼33% of the nucleus tractus solitarius units observed, gastric leptin (10 nM) produced a significant activation of 188.2 ± 8.6% (mean ± SE) compared with the control level of 100% ( P < 0.01). Concentration-dependent leptin effects have also been shown. The remaining neurons (67%) had no significant response to gastric leptin application. Next, we evaluated the peripheral gastric effects of leptin (10 nM) on brain stem unitary activity in three different age groups (1-2 days old, 3-5 days old, and 7-8 days old) of neonatal rats. In the 1- to 2-day-old and the 3- to 5-day-old groups, we observed that response ratios and activity levels were similar. However, there was a significant difference between the 7- to 8-day-old group and the two younger age groups in both the response ratios and the activation levels. The percentage of activation responses increased from ∼26% in the 1- to 2-day-old and the 4- to 5-day-old age groups to 70% in the 7- to 8-day-old group ( P < 0.05). The level of activation increased from 168.3 ± 2.7% (compared with the control level) in the 1- to 2-day-old and the 4- to 5-day-old age groups to 231.4 ± 11.9% in the 7- to 8-day-old group ( P < 0.01). Our data demonstrate that peripheral gastric leptin modulates brain stem neuronal activity and suggest that gastric leptin has a significantly stronger effect in the 7- to 8-day-old animals than in the younger neonates.
Total arterial inertance as the fourth element of the windkessel model.

In earlier studies we found that the three-element windkessel, although an almost perfect load for isolated heart studies, does not lead to accurate estimates of total arterial compliance. To overcome this problem, we introduce an inertial term in parallel with the characteristic impedance. In seven dogs we found that ascending aortic pressure could be predicted better from aortic flow by using the four-element windkessel than by using the three-element windkessel: the root-mean-square errors and the Akaike information criterion and Schwarz criterion were smaller for the four-element windkessel. The three-element windkessel overestimated total arterial compliance compared with the values derived from the area and the pulse pressure method ( P = 0.0047, paired t-test), whereas the four-element windkessel compliance estimates were not different ( P = 0.81). The characteristic impedance was underestimated using the three-element windkessel, whereas the four-element windkessel estimation differed marginally from the averaged impedance modulus at high frequencies ( P = 0.0017 and 0.031, respectively). When applied to the human, the four-element windkessel also was more accurate in these same aspects. Using a distributed model of the systemic arterial tree, we found that the inertial term results from the proper summation of all local inertial terms, and we call it total arterial inertance. We conclude that the fourelement windkessel, with all its elements having a hemodynamic meaning, is superior to the three-element windkessel as a lumped-parameter model of the entire systemic tree or as a model for parameter estimation of vascular properties.
Implications of Patient Portal Transparency in Oncology: Qualitative Interview Study on the Experiences of Patients, Oncologists, and Medical Informaticists

Background Providing patients with unrestricted access to their electronic medical records through patient portals has impacted patient-provider communication and patients’ personal health knowledge. However, little is known about how patient portals are used in oncology. Objective The aim of this study was to understand attitudes of the portal’s adoption for oncology and to identify the advantages and disadvantages of using the portal to communicate and view medical information. Methods In-depth semistructured interviews were conducted with 60 participants: 35 patients, 13 oncologists, and 12 medical informaticists. Interviews were recorded, transcribed, and thematically analyzed to identify critical incidents and general attitudes encountered by participants. Results Two primary themes were discovered: (1) implementation practices influence attitudes, in which the decision-making and execution process of introducing portals throughout the hospital did not include the input of oncologists. Lack of oncologists’ involvement led to a lack of knowledge about portal functionality, such as not knowing the time period when test results would be disclosed to patients; (2) perceptions of portals as communication tools varies by user type, meaning that each participant group (patients, oncologists, and medical informaticists) had varied opinions about how the portal should be used to transmit and receive information. Oncologists and medical informaticists had difficulty understanding one another’s culture and communication processes in their fields, while patients had preferences for how they would like to receive communication, but it largely depended upon the type of test being disclosed. Conclusions The majority of patients (54%, 19/35) who participated in this study viewed lab results or scan reports via the portal before being contacted by a clinician. Most were relatively comfortable with this manner of disclosure but still preferred face-to-face or telephone communication. Findings from this study indicate that portal education is needed for both patients and oncologists, especially when portals are implemented across entire health systems since highly specialized areas of medicine may have unique needs and uses. Patient portals in oncology can potentially alter the way diagnoses are delivered and how patients and oncologists communicate. Therefore, communication about the portal should be established during initial consultations so patients can decide whether they want to be informed in such a manner.
Two types of action potential configuration in single cardiac Purkinje cells of sheep.

Membrane potentials and currents of isolated sheep Purkinje and ventricular cells were compared using patch-clamp and microelectrode techniques. In ∼50% of Purkinje cells, we observed action potentials that showed a prominent phase 1 repolarization and relatively negative plateau (LP cells). Action potential configuration of the remaining Purkinje cells was characterized by little phase 1 repolarization and relatively positive plateau (HP cells). Microelectrode impalement of Purkinje strands also revealed these two types of action potential configuration. In LP cells, the density of L-type Ca2+ current ( I Ca,L) was lower, whereas the density of transient outward K+ current was higher, than in HP cells. Action potentials of HP cells strongly resembled those of ventricular cells. Densities of inward rectifier current and I Ca,L were significantly higher in ventricular cells compared with densities in both LP and HP Purkinje cells. Differences in current densities explain the striking differences in action potential configuration and the stimulus frequency dependency thereof that we observed in LP, HP, and ventricular cells. We conclude that LP Purkinje cells, HP Purkinje cells, and ventricular cells of sheep each have a unique action potential configuration.
Modulation of human airway smooth muscle proliferation by type 3 phosphodiesterase inhibition.

Elevation in cell cAMP content can inhibit mitogenic signaling in cultured human airway smooth muscle (HASM) cells. We studied the effects of the type 3-selective phosphodiesterase inhibitor siguazodan, the type 4-selective phosphodiesterase inhibitor rolipram, and the nonselective inhibitor 3-isobutyl-1-methylxanthine (IBMX) on proliferation of cultured HASM cells. At concentrations selective for the type 3 phosphodiesterase isoform, siguazodan inhibited both [3H]thymidine incorporation (IC50 2 μM) and the increase in cell number (10 μM; 64% reduction) induced by platelet-derived growth factor-BB (20 ng/ml). These effects were mimicked by IBMX. At concentrations selective for type 4 phosphodiesterase inhibition, rolipram was without effect. A 20-min exposure to siguazodan and rolipram did not increase whole cell cAMP levels. However, in HASM cells transfected with a cAMP-responsive luciferase reporter (p6CRE/Luc), increases in cAMP-driven luciferase expression were seen with siguazodan (3.9-fold) and IBMX (16.5-fold). These data suggest that inhibition of the type 3 phosphodiesterase isoform present in airway smooth muscle results in inhibition of mitogenic signaling, possibly through an increase in cAMP-driven gene expression.
Contribution of protein kinase C to ET-1-induced proliferation in human myometrial cells.

The role of protein kinase C (PKC) in endothelin-1 (ET-1)-induced proliferation of human myometrial cells was investigated. ET-1 dose dependently stimulated DNA synthesis and the number of cultured myometrial cells. Inhibition of PKC by calphostin C or Ro-31-8220 or downregulation of PKC eliminated the proliferative effects of ET-1. The failure of two protein tyrosine kinase (PTK) inhibitors (tyrphostin 51 and tyrphostin 23) to affect ET-1-induced proliferation supports the hypothesis of noninvolvement of the tyrosine kinase signaling pathway in this process. The expression and distribution of PKC isoforms were examined by Western blot analysis. The five PKC isoforms (PKC-α, -β1, -β2, -ζ, -ε) evidenced in human myometrial tissue were found to be differentially expressed in myometrial cells, with a predominant expression of PKC-α and PKC-ζ. Treatment with phorbol 12,13-dibutyrate (PDBu) resulted in the translocation of all five isoforms to the particulate fraction, whereas ET-1 induced a selective increase in particulate PKC-β1, PKC-β2, and PKC-ε. Our findings that multiple PKC isoforms are differentially responsive to ET-1 or PDBu suggest that they play distinct roles in the myometrial growth process.
Increased glomerular capillary pressure and size mediate glomerulosclerosis in SHR juxtamedullary cortex.

To gain insight into the mechanisms in the development of glomerulosclerosis in juxtamedullary cortex, the degree of glomerulosclerosis, glomerular tuft diameter, glomerular capillary pressure (Pgc), and local renal blood flow (RBF) autoregulation were measured in superficial and juxtamedullary cortex of 10- and 70-wk-old spontaneously hypertensive rat (SHR), using aged matched Wistar-Kyoto (WKY) rats as controls. Pgc was measured after corticotomy by direct micropuncture of glomeruli in superficial and juxtamedullary cortex. Total RBF was measured by a transit-time flowmeter (Transonic) and local blood flow by use of laser-Doppler flowmetry. The degree of glomerulosclerosis measured by a semiquantitative histological technique was significantly increased in juxtamedullary compared with superficial cortex in all groups. The difference was most pronounced in the juxtamedullary cortex of 70-wk-old SHR. Pgc was significantly increased in juxtamedullary cortex compared with superficial cortex in 70-wk SHR (57.1 ± 2.7 vs. 46.5 ± 0.5 mmHg, P < 0.01). The corresponding data set from 70-wk WKY was 45.5 ± 0.43 vs. 41.6 ± 1.5 ( P < 0.05). The Pgc in juxtamedullary cortex of 10-wk SHR was slightly higher than in superficial cortex (45.1 ± 2.3 vs. 50.1 ± 1.2 mmHg, P = 0.05), whereas there was no difference in 10-wk WKY. Glomerular diameter was larger in juxtamedullary cortex in old animals but not significantly different in 10-wk WKY rats and 10-wk SHR. Total RBF was reset to higher perfusion pressures in hypertensive rats. Juxtamedullary and superficial blood flow autoregulation were not significantly different from total RBF autoregulation in all groups. These results suggest that hypertrophy as well as increased Pgc might contribute to the development of manifest glomerulosclerosis. Changes in local blood flow autoregulation do not seem to play a major role in the development of glomerulosclerosis.
Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders.

To assess muscle remodeling and functional adaptation to exercise and diet interventions, 26 men and women aged 72-98 yr underwent a vastus lateralis biopsy before and after placebo control condition, and progressive resistance training, multinutrient supplementation, or both. Type II atrophy, Z band, and myofibril damage were present at baseline. Combined weight lifting and nutritional supplementation increased strength by 257 ± 62% ( P = 0.0001) and type II fiber area by 10.1 ± 9.0% ( P = 0.033), with a similar trend for type I fiber area (+12.8 ± 22.2%). Exercise was associated with a 2.5-fold increase in neonatal myosin staining ( P = 0.0009) and an increase of 491 ± 137% ( P < 0.0001) in IGF-I staining. Ultrastructural damage increased by 141 ± 59% after exercise training ( P = 0.034). Strength increases were largest in those with the greatest increases in myosin, IGF-I, damage, and caloric intake during the trial. Age-related sarcopenia appears largely confined to type II muscle fibers. Frail elders respond robustly to resistance training with musculoskeletal remodeling, and significant increases in muscle area are possible with resistance training in combination with adequate energy intakes.
Albumin is a major serum survival factor for renal tubular cells and macrophages through scavenging of ROS.

We have previously shown that lysophosphatidic acid (LPA), an abundant serum lipid that binds with high affinity to albumin, is a potent survival factor for mouse proximal tubular cells and peritoneal macrophages. We show here that BSA also has potent survival activity independent of bound lipids. Delipidated BSA (dBSA) protected cells from apoptosis induced by FCS withdrawal at concentrations as low as 1% of that in FCS. dBSA did not activate phosphatidylinositol 3-kinase, implying that its survival activity occurs via a mechanism distinct from that for most cytokines. On the basis of the following evidence, we propose that dBSA inhibits apoptosis by scavenging reactive oxygen species (ROS): 1) FCS withdrawal leads to ROS accumulation that is inhibitable by dBSA; 2) during protection from apoptosis, sulfhydryl and hydroxyl groups of dBSA are oxidized; and 3) chemical blockage of free sulfhydryl groups or preoxidation of dBSA with H2O2removes its survival activity. Moreover, dBSA confers almost complete protection from cell death in a well-established model of oxidative injury (xanthine/xanthine oxidase). These results implicate albumin as a major serum survival factor. Inhibition of apoptosis by albumin occurs through at least two distinct mechanisms: carriage of LPA and scavenging of ROS.
Leptin depolarizes rat hypothalamic paraventricular nucleus neurons.

Leptin, the protein product of the ob/ obgene, is thought to have a central site of action, presumably within the hypothalamus, through which it regulates feeding behavior. The paraventricular nucleus (PVN) is one structure that has been implicated in regulating feeding behavior. Using patch-clamp recording techniques, this study examines the direct membrane effects of leptin on neurons in a coronal PVN slice. Bath application of the physiologically active leptin fragment (amino acids 22-56) elicited dose-related depolarizations in 82% of the type I cells tested ( n = 17) and 67% of the type II cells tested ( n = 9). By contrast, the physiologically inactive leptin fragment (amino acids 57-92) had no discernible effect on membrane potential ( n = 7). The effects of this peptide were unaffected following synaptic isolation of the cells by bath application of the sodium channel blocker tetrodotoxin ( n = 5). Voltage clamp recordings in six cells demonstrated that leptin increased a nonspecific cation conductance with a reversal potential near -30 mV. These findings suggest that neurons in PVN may play an important role in the central neuronal circuitry involved in the physiological response to leptin.
c-Fos induction in spinal cord neurons after renal arterial or venous occlusion.

Experiments were done in the anesthetized rat to identify the dorsal root ganglia (DRG) and the spinal cord segments that contain neurons activated by either renal venous occlusion (RVO) or by renal arterial occlusion (RAO). Fos induction, detected immunohistochemically in DRG and the spinal cord neurons, was used as a marker for neuronal activation. RVO induced Fos immunoreactivity in neurons in the DRG of spinal segments T8-L2on the side ipsilateral to that of occlusion. The largest number of Fos-labeled neurons was found in the T11 DRG. In the spinal cord the largest number of Fos-labeled neurons was found in the ipsilateral dorsal horn of spinal segments T11-T12, predominantly in a cluster near the dorsomedial edge of laminae I-II. A few additional Fos-labeled neurons were observed in laminae IV and V. After RAO Fos-labeled neurons were found in the ipsilateral DRG of spinal segments similar to those observed to contain neurons after RVO. However, most of the Fos-labeled neurons were observed within the T12-L1DRG. In the spinal cord Fos-labeled neurons were scattered throughout lamina I-II of the ipsilateral dorsal horn of spinal segments T8-L2, although the largest number was observed at the T13 level. Additionally, a distinct cluster of Fos-labeled neurons was observed predominantly in the region of the ipsilateral intermediolateral cell column, although a few neurons were found scattered throughout the nucleus intercalatus, central autonomic areas, and laminae IV and V of the cord bilaterally. No Fos labeling was observed in the complementary contralateral DRG or dorsal horns after either RVO or RAO. In addition, renal nerve transection prevented Fos labeling in the ipsilateral DRG and dorsal horns after RVO or RAO. Taken together, these data suggest that functionally different renal afferent fibers activate DRG neurons that may have distinct projections in the spinal cord.
Microtubule disruption inhibits AVT-stimulated Cl- secretion but not Na+ reabsorption in A6 cells.

The effects of microtubule disruption on arginine vasotocin (AVT)-stimulated Na+ and Cl- transport were studied in A6 cells by measuring short-circuit currents ( I sc) across cell layers grown in tissue culture on permeable supports. Microtubule disruption inhibited an AVT-stimulated secretory Cl- current but did not prevent activation of amiloride-sensitive Na+ transport. This AVT-stimulated secretory Cl- current was significantly inhibited by glibenclamide, an inhibitor of the cystic fibrosis transmembrane conductance regulator (CFTR). Reverse transcription of RNA isolated from A6 cells followed by polymerase chain reaction (PCR) using primers designed to amplify a portion of the R-domain of CFTR cloned from Xenopus laevis skin and immunocytochemistry demonstrated the presence of CFTR in A6 cells and an apparent recruitment of cytoplasmic CFTR to the apical cell surface after AVT stimulation. In contrast, indirect immunofluorescent labeling of Na+ channels using a polyclonal antibody raised against a biochemically isolated Na+ channel complex from bovine renal medulla labeled the apical plasma membrane but failed to demonstrate intracellular labeling of Na+ channels (except in subconfluent cells) or recruitment of Na+ channels to the apical membrane region after AVT stimulation.
Combining acceleration and gyroscope data for motion gesture recognition using classifiers with dimensionality constraints

Motivated by the addition of gyroscopes to a large number of new smart phones, we study the effects of combining accelerometer and gyroscope data on the recognition rate of motion gesture recognizers with dimensionality constraints. Using a large data set of motion gestures we analyze results for the following algorithms: Protractor3D, Dynamic Time Warping (DTW) and Regularized Logistic Regression (LR). We chose to study these algorithms because they are relatively easy to implement, thus well suited for rapid prototyping or early deployment during prototyping stages. For use in our analysis, we contribute a method to extend Protractor3D to work with the 6D data obtained by combining accelerometer and gyroscope data. Our results show that combining accelerometer and gyroscope data is beneficial also for algorithms with dimensionality constraints and improves the gesture recognition rate on our data set by up to 4%.
Asbestos exposure upregulates the adhesion of pleural leukocytes to pleural mesothelial cells via VCAM-1.

This study was designed to assess the effects of in vitro and in vivo asbestos exposure on the adhesion of rat pleural leukocytes (RPLs) labeled with the fluorochrome calcein AM to rat pleural mesothelial cells (RPMCs). Exposure of RPMCs for 24 h to either crocidolite or chrysotile fibers (1.25-10 μg/cm2) increased the adhesion of RPLs to RPMCs in a dose-dependent fashion, an effect that was potentiated by interleukin-1β. These findings were not observed with nonfibrogenic carbonyl iron particles. Crocidolite and chrysotile plus interleukin-1β also upregulated vascular cell adhesion molecule-1 mRNA and protein expression in RPMCs, and the binding of RPL to asbestos-treated RPMCs was abrogated by anti-vascular cell adhesion molecule-1 antibody. PRLs exposed by intermittent inhalation to crocidolite for 2 wk manifested significantly greater binding to RPMCs than did RPLs from sham-exposed animals. The ability of asbestos fibers to upregulate RPL adhesion to RPMCs may play a role in the induction and/or potentiation of asbestos-induced pleural injury.
Volume-dependent taurine release from cultured astrocytes requires permissive [Ca2+]iand calmodulin.

Cell swelling results in regulatory activation of multiple conductive anion pathways permeable toward a broad spectrum of intracellular organic osmolytes. Here, we explore the involvement of extracellular and intracellular Ca2+ in volume-dependent [3H]taurine efflux from primary cultured astrocytes and compare the Ca2+ sensitivity of this efflux in slow (high K+ medium induced) and fast (hyposmotic medium induced) cell swelling. Neither Ca2+-free medium nor Ca2+-channel blockers prevented the volume-dependent [3H]taurine release. In contrast, loading cells with the membrane-permeable Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane- N, N, N', N'-tetraacetic acid (BAPTA)-AM suppressed [3H]taurine efflux by 65-70% and 25-30% under high-K+ and hyposmotic conditions, respectively. Fura 2 measurements confirmed that BAPTA-AM, but not Ca2+-free media, significantly reduced resting intracellular Ca2+concentration ([Ca2+]i). The calmodulin antagonists trifluoperazine and fluphenazine reversibly and irreversibly, respectively, inhibited the high-K+-induced [3H]taurine release, consistent with their known actions on calmodulin. In hyposmotic conditions, the effects were less pronounced. These data suggest that volume-dependent taurine release requires minimal basal [Ca2+]iand involves calmodulin-dependent step(s). Quantitative differences in Ca2+/calmodulin sensitivity of high-K+-induced and hyposmotic medium-induced taurine efflux are due to both the effects of the inhibitors on high-K+-induced cell swelling and their effects on transport systems and/or signaling mechanisms determining taurine efflux.