Functional dynamics and selectivity of two parallel corticocortical pathways from motor cortex to layer 5 circuits in somatosensory cortex.

In the rodent whisker system, active sensing and sensorimotor integration are mediated in part by the dynamic interactions between the motor cortex (M1) and somatosensory cortex (S1). However, understanding these dynamic interactions requires knowledge about the synapses and how specific neurons respond to their input. Here, we combined optogenetics, retrograde labeling, and electrophysiology to characterize the synaptic connections between M1 and layer 5 (L5) intratelencephalic (IT) and pyramidal tract (PT) neurons in S1 of mice (both sexes). We found that M1 synapses onto IT cells displayed modest short-term depression, whereas synapses onto PT neurons showed robust short-term facilitation. Despite M1 inputs to IT cells depressing, their slower kinetics resulted in summation and a response that increased during short trains. In contrast, summation was minimal in PT neurons due to the fast time course of their M1 responses. The functional consequences of this reduced summation, however, were outweighed by the strong facilitation at these M1 synapses, resulting in larger response amplitudes in PT neurons than IT cells during repetitive stimulation. To understand the impact of facilitating M1 inputs on PT output, we paired trains of inputs with single backpropagating action potentials, finding that repetitive M1 activation increased the probability of bursts in PT cells without impacting the time-dependence of this coupling. Thus, there are two parallel but dynamically distinct systems of M1 synaptic excitation in L5 of S1, each defined by the short-term dynamics of its synapses, the class of postsynaptic neurons, and how the neurons respond to those inputs.

Antiobesity Effects of Lactobacillus paracasei Subsp. paracasei, L. casei 431 on High-Fat Diet-Induced Obese Rats.

Obesity is currently regarded as a global concern, and the key objectives of the global health strategy include its prevention and control. Probiotic supplementation can help achieve these objectives. This study aimed to assess whether a probiotic strain Lactobacillus paracasei ssp. paracasei, Lactobacillus casei 431 (henceforth, L. casei 431) possesses antiobesogenic properties. High-fat diet-induced obese Sprague-Dawley rats were treated with L. casei 431 for 10 weeks, and the outcomes were compared with those of rats treated with the antiobesity medication orlistat. Body weights, epididymal fat, and tissues from mice were assessed. Furthermore, serological and histological analyses were performed. Epididymal fat accumulation was significantly reduced in groups administered L. casei 431 and orlistat. Furthermore, L. casei 431 and orlistat treatments lowered serum alanine transaminase, aspartate aminotransferase, and triglyceride (TG) levels. Hematoxylin and eosin staining of the liver and epididymal adipose tissues showed that the L. casei 431-treated groups exhibited reduced lipid buildup and adipocyte size. Furthermore, sterol regulatory element-binding protein 1c, adipose TG lipase, and lipoprotein lipase messenger RNA (mRNA) levels were upregulated, leading to lipid oxidation and degradation, in L. casei 431-supplemented groups. Furthermore, carnitine palmitoyltransferase 1, a major factor in lipolysis, was consistently upregulated at the protein level after L. casei 431 administration. Collectively, these results demonstrate the potential of L. casei 431 in alleviating obesity in rats through optimizing lipid metabolism and some related biomarkers.

A simple urine test by 3D-plus-3D immunoassay guides precise in vitro cancer diagnosis.

Although a variety of urinary cancer markers are available for in vitro diagnosis, inherent problems of urine environment-containing various inorganic/organic ions/molecules that vary in concentration over a 20-fold range or more and significantly attenuate antibody avidity for markers-render conventional immunoassays unsuitable, remaining unresolved and a major challenge. Here we developed a 3D-plus-3D (3p3) immunoassay method, based on a single-step urinary marker detection by 3D-antibody probes, which are free of steric hindrance and capable of omnidirectional capture of markers in a 3D solution. The 3p3 immunoassay showed an excellent performance in the diagnosis of prostate cancer (PCa) through detecting PCa-specific urinary engrailed-2 protein, demonstrating 100% sensitivity and 100% specificity with the urine specimens of PCa-related and other related disease patients and healthy individuals. This innovative approach holds a great potential in opening up a novel clinical route for precise in vitro cancer diagnosis and also pushing urine immunoassay closer to more widespread adoption.

Short-Term Facilitation of Long-Range Corticocortical Synapses Revealed by Selective Optical Stimulation.

Short-term plasticity regulates the strength of central synapses as a function of previous activity. In the neocortex, direct synaptic interactions between areas play a central role in cognitive function, but the activity-dependent regulation of these long-range corticocortical connections and their impact on a postsynaptic target neuron is unclear. Here, we use an optogenetic strategy to study the connections between mouse primary somatosensory and motor cortex. We found that short-term facilitation was strong in both corticocortical synapses, resulting in far more sustained responses than local intracortical and thalamocortical connections. A major difference between pathways was that the synaptic strength and magnitude of facilitation were distinct for individual excitatory cells located across all cortical layers and specific subtypes of GABAergic neurons. Facilitation was dependent on the presynaptic calcium sensor synaptotagmin-7 and altered by several optogenetic approaches. Current-clamp recordings revealed that during repetitive activation, the short-term dynamics of corticocortical synapses enhanced the excitability of layer 2/3 pyramidal neurons, increasing the probability of spiking with activity. Furthermore, the properties of the connections linking primary with secondary somatosensory cortex resemble those between somatosensory-motor areas. These short-term changes in transmission properties suggest long-range corticocortical synapses are specialized for conveying information over relatively extended periods.

Dopamine Receptor Supports the Potentiation of Intrinsic Excitability and Synaptic LTD in Temporoammonic-CA1 Synapse.

Dopaminergic projection to the hippocampus from the ventral tegmental area or locus ceruleus has been considered to play an essential role in the acquisition of novel information. Hence, the dopaminergic modulation of synaptic plasticity in the hippocampus has been widely studied. We examined how the D1 and D2 receptors influenced the mGluR5-mediated synaptic plasticity of the temporoammonic-CA1 synapses and showed that the dopaminergic modulation of the temporoammonic-CA1 synapses was expressed in various ways. Our findings suggest that the dopaminergic system in the hippocampal CA1 region regulates the long-term synaptic plasticity and processing of the novel information.

One-step-immunoassay of procalcitonin enables rapid and accurate diagnosis of bacterial infection.

Procalcitonin (PCT) (i.e. a precursor of calcitonin) attracts much attention as a reliable biomarker of bacterial infections because its concentration increases rapidly in the blood when bacterial infections occur in the body. Sepsis may occur due to indiscriminate and vigorous proliferation of infectious bacteria, and accordingly early diagnosis and treatment of bacterial infection are of crucial importance. However, current diagnostic methods for sepsis suffer from long assay time, multiple and complex assay steps, inaccuracy, and requirement of analytical equipments. The goal of this study is to develop an advanced one-step-immunoassay that enables quick and accurate diagnosis of sepsis through measuring the PCT concentration in patient sera, which is based on self-enhancement of optical detection signals from large gold particles (i.e. clusters of gold nanoparticles) that are formed on the agglomerates of PCT-bound 3-dimensional (3D) probes. The 3D probe is constructed through attaching polyclonal anti-PCT antibodies (IgGs) to the surface of a modified hepatitis B virus (HBV) capsid, where both tandem repeats of the B domain of Staphylococcal protein A (SPAB) and the hexa-histidine tag are inserted into each HBV core protein (i.e. subunit of HBV capsid). That is, anti-PCT IgGs are attached via strong interaction between the Fc region and surface-exposed SPAB. Furthermore, hook effect-free and PCT concentration-dependent optical signals were consistently generated by adding both bovine serum albumin (BSA) and nickel ions to patient sera and also by optimally adjusting the 3D probe concentration. Compared to conventional chemiluminescent microparticle immunoassay (CMIA) showing poor linearity of detection signals, this novel immunoassay accurately detected PCT with good linearity between PCT concentrations and optical signals in a wide range of PCT concentrations (0.05-200 ng mL-1) and also showed a sufficiently low limit of detection, resulting in 100% sensitivity and 100% specificity when tested with 30 sepsis patients and 30 healthy individuals.

Stabilization of Fibronectin by Random Copolymer Brushes Inhibits Macrophage Activation.

We show that protein unfolding on biomaterials may be dramatically reduced via tuning the chemical heterogeneity of the protein-material interface. Specifically, using dynamic single-molecule methods, we confirmed that the transient structure and dynamics of fibronectin (FN) may be mediated through varying the composition of random copolymer brushes. The brushes, which themselves represent an intriguing biomaterial, were composed of oligoethylene glycol and sulfobetaine methacrylate and presumably stabilized FN through partitioning and/or segregation of the copolymers. We further showed that, by controlling the transient structure and dynamics of FN, the secretion of TNF-α and IL-6 by RAW 264.7 was markedly diminished.

Association of mGluR-Dependent LTD of Excitatory Synapses with Endocannabinoid-Dependent LTD of Inhibitory Synapses Leads to EPSP to Spike Potentiation in CA1 Pyramidal Neurons.

The input-output relationships in neural circuits are determined not only by synaptic efficacy but also by neuronal excitability. Activity-dependent alterations of synaptic efficacy have been extensively investigated, but relatively less is known about how the neuronal output is modulated when synaptic efficacy changes are associated with neuronal excitability changes. In this study, we demonstrate that paired pulses of low-frequency stimulation (PP-LFS) induced metabotropic glutamate receptor (mGluR)-dependent LTD at Schaffer collateral (SC)-CA1 synapses in Sprague Dawley rats (both sexes), and this LTD was associated with EPSP to spike (E-S) potentiation, leading to the increase in action potential (AP) outputs. Threshold voltage (Vth) for APs evoked by synaptic stimulation and that by somatic current injection were hyperpolarized significantly after PP-LFS. Blockers of GABA receptors mimicked and occluded PP-LFS effects on E-S potentiation and Vth hyperpolarization, suggesting that suppression of GABAergic mechanisms is involved in E-S potentiation after PP-LFS. Indeed, IPSCs and tonic inhibitory currents were reduced after PP-LFS. The IPSC reduction was accompanied by increased paired-pulse ratio, and abolished by AM251, a blocker for Type 1 cannabinoid receptors, suggesting that PP-LFS suppresses presynaptic GABA release by mGluR-dependent endocannabinoids signaling. By contrast, a Group 1 mGluR agonist, 3, 5-dihydroxyphenylglycine, induced LTD at SC-CA1 synapses but failed to induce significant IPSC reduction and AP output increase. We propose that mGluR signaling that induces LTD coexpression at excitatory and inhibitory synapses regulates an excitation-inhibition balance to increase neuronal output in CA1 neurons.SIGNIFICANCE STATEMENT Long-lasting forms of synaptic plasticity are usually associated with excitability changes, the ability to fire action potentials. However, excitability changes have been regarded to play subsidiary roles to synaptic plasticity in modifying neuronal output. We demonstrate that, when metabotropic glutamate receptor-dependent LTD is induced by paired pulses of low-frequency stimulation, the action potential output in response to a given input paradoxically increases, indicating that increased excitability is more powerful than synaptic depression. This increase is mediated by the suppression of a presynaptic GABA release via metabotropic glutamate receptor-dependent endocannabinoid signaling. Our study shows that neuronal output changes do not always follow the direction of synaptic plasticity at excitatory synapses, highlighting the importance of regulating inhibitory tone via endocannabinoid signaling.

Thermal and Optical Performance of Glass Cloth Reinforced Organic-Inorganic Hybrid Polymer Composite Film.

Recently there has been considerable interest in flexible display as the next-generation display. The flexible plastic has been recommended as a strong candidate for substrate, but these plastic substrates have many problems to provide the comparable properties of dimensional stability, thermal stability, and solvent resistance to glass in order to apply conventional thin film transistor technology to flexible display. Then in this study, a glass cloth reinforced polymer (GCRP) composite was prepared. To improve the thermal property, glass cloth with an excellent coefficient of thermal expansion (CTE) for reinforcement and organic-inorganic hybrid nanomaterial with polyhedral oligomeric silsesquioxane (POSS) material having excellent heat resistance were introduced to ensure the excellent properties like transmittance, haze, yellow index, thermal stability and chemical resistance. The optical property of GCRP composite was measured by using a spectrophotometer and the CTE of GCRP composite was observed by thermomechanical analysis (TMA).

Chitosan as a stabilizer and size-control agent for synthesis of porous flower-shaped palladium nanoparticles and their applications on photo-based therapies.

This study reported a newly developed green synthesis method using chitosan and vitamin C to prepare porous flower-shaped palladium nanoparticles. We found that chitosan not only worked as a stabilizer but also as a size-control agent for the synthesis of these nanoparticles. The growth model of flower-shaped palladium nanoparticles was proposed to interpret mechanistic understanding. The obtained nanoparticles showed good biocompatibility and strong near-infrared absorption. The nanoparticles were successfully demonstrated to be highly efficient for both in vitro photothermal therapy and in vitro photoacoustic imaging.

Endocytosis of KATP Channels Drives Glucose-Stimulated Excitation of Pancreatic ß Cells.

Insulin secretion from pancreatic ß cells in response to high glucose (HG) critically depends on the inhibition of KATP channel activity in HG. It is generally believed that HG-induced effects are mediated by the increase in intracellular ATP, but here, we showed that, in INS-1 cells, endocytosis of KATP channel plays a major role. Upon HG stimulation, resting membrane potential depolarized by 30.6 mV (from -69.2 to -38.6 mV) and KATP conductance decreased by 91% (from 0.243 to 0.022 nS/pF), whereas intracellular ATP was increased by only 47%. HG stimulation induced internalization of KATP channels, causing a significant decrease in surface channel density, and this decrease was completely abolished by inhibiting endocytosis using dynasore, a dynamin inhibitor, or a PKC inhibitor. These drugs profoundly inhibited HG-induced depolarization. Our results suggest that the control of KATP channel surface density plays a greater role than ATP-dependent gating in regulating ß cell excitability.

Hydroxyapatite Coated Iron Oxide Nanoparticles: A Promising Nanomaterial for Magnetic Hyperthermia Cancer Treatment.

Targeting cancer cells without injuring normal cells is the prime objective in treatment of cancer. In this present study, solvothermal and wet chemical precipitation techniques were employed to synthesize iron oxide (IO), hydroxyapatite (HAp), and hydroxyapatite coated iron oxide (IO-HAp) nanoparticles for magnetic hyperthermia mediated cancer therapy. The synthesized well dispersed spherical IO-HAp nanoparticles, magnetite, and apatite phases were confirmed by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and Field emission transmission electron microscopy (FETEM) with Energy Dispersive X-ray spectroscopy (EDS). The non-toxic behavior of synthesized IO-HAp nanoparticles was confirmed by cytotoxicity assay (Trypan blue and MTT assay). The synthesized nanoparticles revealed a remarkable magnetic saturation of 83.2 emu/g for IO and 40.6 emu/g for IO-HAp nanoparticles in presence of 15,000 Oe (1.5 T) magnetic field at room temperature (300 K). The magnetic hyperthermia study that was performed with IO-HAp nanoparticles showed an excellent hyperthermia effect (SAR value 85 W/g) over MG-63 osteosarcoma cells. The in vitro hyperthermia temperature (~45 °C) was reached within 3 min, which shows a very high efficiency and kills nearly all of the experimental MG-63 osteosarcoma cells within 30 min exposure. These results could potentially open new perceptions for biomaterials that are aimed for anti-cancer therapies based on magnetic hyperthermia.

Magnetic hydroxyapatite: a promising multifunctional platform for nanomedicine application.

In this review, specific attention is paid to the development of nanostructured magnetic hydroxyapatite (MHAp) and its potential application in controlled drug/gene delivery, tissue engineering, magnetic hyperthermia treatment, and the development of contrast agents for magnetic resonance imaging. Both magnetite and hydroxyapatite materials have excellent prospects in nanomedicine with multifunctional therapeutic approaches. To date, many research articles have focused on biomedical applications of nanomaterials because of which it is very difficult to focus on any particular type of nanomaterial. This study is possibly the first effort to emphasize on the comprehensive assessment of MHAp nanostructures for biomedical applications supported with very recent experimental studies. From basic concepts to the real-life applications, the relevant characteristics of magnetic biomaterials are patented which are briefly discussed. The potential therapeutic and diagnostic ability of MHAp-nanostructured materials make them an ideal platform for future nanomedicine. We hope that this advanced review will provide a better understanding of MHAp and its important features to utilize it as a promising material for multifunctional biomedical applications.

Costimulation of AMPA and metabotropic glutamate receptors underlies phospholipase C activation by glutamate in hippocampus.

Glutamate, a major neurotransmitter in the brain, activates ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs, respectively). The two types of glutamate receptors interact with each other, as exemplified by the modulation of iGluRs by mGluRs. However, the other way of interaction (i.e., modulation of mGluRs by iGluRs) has not received much attention. In this study, we found that group I mGluR-specific agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) alone is not sufficient to activate phospholipase C (PLC) in rat hippocampus, while glutamate robustly activates PLC. These results suggested that additional mechanisms provided by iGluRs are involved in group I mGluR-mediated PLC activation. A series of experiments demonstrated that glutamate-induced PLC activation is mediated by mGluR5 and is facilitated by local Ca(2+) signals that are induced by AMPA-mediated depolarization and L-type Ca(2+) channel activation. Finally, we found that PLC and L-type Ca(2+) channels are involved in hippocampal mGluR-dependent long-term depression (mGluR-LTD) induced by paired-pulse low-frequency stimulation, but not in DHPG-induced chemical LTD. Together, we propose that AMPA receptors initiate Ca(2+) influx via the L-type Ca(2+) channels that facilitate mGluR5-PLC signaling cascades, which underlie mGluR-LTD in rat hippocampus.

Effective intervention strategies to improve health outcomes for cardiovascular disease patients with low health literacy skills: a systematic review.

PURPOSE: Systematic studies on the relationship between health literacy and health outcomes demonstrate that as health literacy declines, patients engage in fewer preventive health and self-care behaviors and have worse disease-related knowledge. The purpose of this study was to identify effective intervention strategies to improve health outcomes in patients with cardiovascular disease and low literacy skills. METHODS: This study employs the following criteria recommended by Khan Kunz, Keijnen, and Antes (2003) for systematic review: framing question, identifying relevant literature, assessing quality of the literature, summarizing the evidence, and interpreting the finding. A total of 235 articles were reviewed by the research team, and 9 articles met inclusion criteria. Although nine studies were reviewed for their health outcomes, only six studies, which had a positive quality grade evaluation were used to recommend effective intervention strategies. RESULTS: Interventions were categorized into three groups: tailored counseling, self-monitoring, and periodic reminder. The main strategies used to improve health outcomes of low literacy patients included tailored counseling, improved provider-patient interactions, organizing information by patient preference, self-care algorithms, and self-directed learning. Specific strategies included written materials tailored to appropriate reading levels, materials using plain language, emphasizing key points with large font size, and using visual items such as icons or color codes. CONCLUSION: With evidence-driven strategies, health care professionals can use tailored interventions to provide better health education and counseling that meets patient needs and improves health outcomes.

[Suitability and readability assessment of printed educational materials on hypertension].

PURPOSE: The aim of this study was to assess the suitability and readability of printed educational materials for patients with hypertension in Korea. METHODS: A total of 33 written educational materials related to hypertension were collected from public health centers, hospitals, and internet web site. Among them, we analyzed 19 materials which fit the inclusion criteria: leaflets (n=9), booklets (n=3), and guide book (n=7). Two trained nurses evaluate the materials using suitability assessment tool (SAM; Doak, Doak, & Root, 1996a) and graded lexical items for teaching Korean (Kim, 2003). RESULTS: Overall, 14 (73.7%) of 19 materials scored adequate, and 5 (26.3%) scored inadequate. On the average, the education materials contained 36.1% to 50.5% of 1st grade reading level words and 12.9% to 21.6% of 4th grade level and over. CONCLUSION: The reading level of the materials was higher than a 6th grade reading level. It is proposed that the written educational materials should be developed by health professionals according to suitability and quality by taking the target group's literacy capacity into consideration.

Organization of calbindin D28K-immunoreactive neurons in the dog superior colliculus.

We localized calbindin D28K-immunoreactive (IR) neurons in the superior colliculus (SC) of the dog and studied the distribution and effect of enucleation on the distribution of this protein. We also compared this labeling to that of GABA. Calbindin D28K was localized with antibody immunocytochemistry. Calbindin D28K-IR neurons formed three laminar tiers in the SC, one within the lower superficial gray layer (SGL), the second within the upper intermediate gray layers (IGL), and the third within the deep gray layer (DGL). The third tier was not very distinctive when compared with the other two tiers. Calbindin D28K-IR neurons in the SC varied dramatically in morphology and size, and included round/oval, vertical fusiform, stellate, pyriform, and horizontal neurons. Neurons with varicose dendrite were also labeled in the IGL. Enucleation appeared to have no effect on the distribution of calbindin D28K-IR neurons in the contralateral SC. Two-color immunofluorescence revealed that a small percentage (11.20%) of calbindin D28K-IR neurons co-localized with GABA. The current results demonstrate that the patterned distribution of calbindin D28K-IR neurons in the intermediate and deep SC is comparable with other animals, but that the distribution of this protein in the superficial SC is strikingly different from that in previously studied animals. The results also suggest that retinal projection may not control the activity of the expression of calbindin D28K in the dog SC. These results will not only provide valuable knowledge of the basic neurochemical architecture of the dog visual system, but also provide clues for the understanding of the similarities and differences among species.