Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex.

Diverse neocortical GABAergic neurons specialize in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in 2 distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBCs) had columnar "horsetail" axons descending through layers II-V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and nonpyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%), and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline) but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialized, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex.

Influence of vitamin D receptor polymorphism rs2228570 on pathological scarring.

The physiological process of scarring is a common denominator of interest in a plethora of medical specialties. The molecular basis whereby this process results in pathological scarring for some individuals is poorly understood at present, with clues pointing towards individual predisposition for pathological scarring. Vitamin D and its subsequent pathway plays a key role in skin metabolism and homeostasis, with alterations in the level of vitamin D receptor (VDR) seen within pathological scars. The present study investigated the role of the rs2228570 polymorphism of VDR with regards to scar formation and evolution in a group of 71 female patients recovering from Caesarian section. Blood samples were taken at the time of surgery, and the follow-up was collected remotely at 3 and 6 months after surgery. The rs2228570 polymorphism was investigated using an RFLP-PCR protocol. The results demonstrated that the CC genotype, in combination with the Patient Observer Scar Assessment Scale (POSAS) and SCAR scores are associated with pathological scarring, with more studies being necessary to draw a firm conclusion.

Role of hTERT rs2736100 in pathological scarring.

Hypertrophic and atrophic scars are the effect of a dysregulated wound-healing process in genetically predisposed individuals. The genetic predisposition has acquired significant attention due to the diverse phenotype of pathological scarring in individuals with a positive personal and family history. Recent studies have identified telomere shortening and decreased hTERT activity in pathological scarring, proposing the rs2736100 variant of human telomerase reverse transcriptase (hTERT) gene as a valuable variant gene candidate. We examined the scarring process in 71 female patients who had undergone Caesarean section and developed hypertrophic and atrophic scars with the objective to investigate the role of single nucleotide polymorphism (SNP) rs2736100 in pathological scarring. Genotyping was performed using RT-PCR and follow-up included the Patient Observer Scar Assessment Scale (POSAS) and SCAR scales. Comparative analysis for mean POSAS value between the check-ups at 3 and 6 months revealed a statistical decreased difference of 1.71 points [95% confidence interval (CI), 0.4-2.89; P=0.01], while SCAR highlighted a decreased difference of 0.670 (95% CI, -0.04-1.38; P=0.055). The C variant allele revealed a borderline statistical value for the risk of developing pathological scarring (OR=1.44; 95% CI, 0.876-1.332: P=0.066). In our study a pre-conceptional body mass index (BMI) >25 kg/m2 was statistically associated with pathological scarring. The Fitzpatrick type 4 phototype displayed an increased frequency for the heterozygous genotype in the current study, and it was demonstrated that dark skin tone was associated with abnormal scar formation. Our study investigated the role of hTERT gene variant rs2736100 in hypertrophic and atrophic scarring in a Caucasian population group. We report a borderline statistically significant value for the variant C allele of hTERT SNP for the risk of developing pathological scarring in female patients that had undergone Caesarean section.

Gate-Controlled Supercurrent in Epitaxial Al/InAs Nanowires.

Gate-controlled supercurrent (GCS) in superconducting nanobridges has recently attracted attention as a means to create superconducting switches. Despite the clear advantages for applications, the microscopic mechanism of this effect is still under debate. In this work, we realize GCS for the first time in a highly crystalline superconductor epitaxially grown on an InAs nanowire. We show that the supercurrent in the epitaxial Al layer can be switched to the normal state by applying ≃±23 V on a bottom gate insulated from the nanowire by a crystalline hBN layer. Our extensive study of the temperature and magnetic field dependencies suggests that the electric field is unlikely to be the origin of GCS in our device. Though hot electron injection alone cannot explain our experimental findings, a very recent non-equilibrium phonons based picture is compatible with most of our results.

Tonic GABAA Receptor-Mediated Currents of Human Cortical GABAergic Interneurons Vary Amongst Cell Types.

Persistent anion conductances through GABAA receptors (GABAARs) are important modulators of neuronal excitability. However, it is currently unknown how the amplitudes of these currents vary among different cell types in the human neocortex, particularly among diverse GABAergic interneurons. We have recorded 101 interneurons in and near layer 1 from cortical tissue surgically resected from both male and female patients, visualized 84 of them and measured tonic GABAAR currents in 48 cells with an intracellular [Cl-] of 65 mm and in the presence of 5 µm GABA. We compare these tonic currents among five groups of interneurons divided by firing properties and four types of interneuron defined by axonal distributions; rosehip, neurogliaform, stalked-bouton, layer 2-3 innervating and a pool of other cells. Interestingly, the rosehip cell, a type of interneuron only described thus far in human tissue, and layer 2-3 innervating cells exhibit larger tonic currents than other layer 1 interneurons, such as neurogliaform and stalked-bouton cells; the latter two groups showing no difference. The positive allosteric modulators of GABAARs allopregnanolone and DS2 also induced larger current shifts in the rosehip and layer 2-3 innervating cells, consistent with higher expression of the δ subunit of the GABAAR in these neurons. We have also examined how patient parameters, such as age, seizures, type of cancer and anticonvulsant treatment may alter tonic inhibitory currents in human neurons. The cell type-specific differences in tonic inhibitory currents could potentially be used to selectively modulate cortical circuitry.SIGNIFICANCE STATEMENT Tonic currents through GABAA receptors (GABAARs) are a potential therapeutic target for a number of neurologic and psychiatric conditions. Here, we show that these currents in human cerebral cortical GABAergic neurons display cell type-specific differences in their amplitudes which implies differential modulation of their excitability. Additionally, we examine whether the amplitudes of the tonic currents measured in our study show any differences between patient populations, finding some evidence that age, seizures, type of cancer, and anticonvulsant treatment may alter tonic inhibition in human tissue. These results advance our understanding of how pathology affects neuronal excitability and could potentially be used to selectively modulate cortical circuitry.

Andreev Molecule in Parallel InAs Nanowires.

Coupling individual atoms fundamentally changes the state of matter: electrons bound to atomic cores become delocalized turning an insulating state to a metallic one. A chain of atoms could lead to more exotic states if the tunneling takes place via the superconducting vacuum and can induce topologically protected excitations like Majorana or parafermions. Although coupling a single atom to a superconductor is well studied, the hybridization of two sites with individual tunability was not reported yet. The peculiar vacuum of the Bardeen-Cooper-Schrieffer (BCS) condensate opens the way to annihilate or generate two electrons from the bulk resulting in a so-called Andreev molecular state. By employing parallel nanowires with an Al shell, two artificial atoms were created at a minimal distance with an epitaxial superconducting link between. Hybridization via the BCS vacuum was observed and the spectrum of an Andreev molecule as a function of level positions was explored for the first time.

Involvement of COL5A2 and TGF-ß1 in pathological scarring.

Dysregulation in the cutaneous wound-healing process is a consequence of alterations in the efficiency and activity of the various components involved in the healing process. This dysregulation may result in various clinical appearances of a lesion, such as skin ulcers, keloids, hypertrophic and atrophic scars. The collagen type V alpha 2 (COL5A2) gene provides a template for a component of type V collagen, found primarily within the skin basement membrane. Transforming growth factor (TGF)-ß is involved in inflammation, angiogenesis, proliferation of fibroblasts, collagen synthesis and extracellular matrix remodeling. Hypertrophic scar fibroblasts possess a disrupted expression pattern of the TGF-ß signaling compared to normal healing, while an increased TGF-ß signaling reduces the epidermal proliferation rate, triggering atrophic scarring. In the present study, 71 female patients who had undergone planned Caesarean section, without postoperative complications, were examined. These patients were clinically and molecularly evaluated after developing scars in order to determine the role of TGF-ß1 (rs201700967 and rs200230083) and COL5A2 (rs369072636) in pathological scarring. Clinical scar evaluation was carried out using SCAR and POSAS scales and genotyping was performed by RT-PCR. No statistical differences were found between the subgroups regarding the genotype and the pathological scarring, since all the patients included were wild-type allele carriers. Further investigations and a more representative study group may highlight the involvement of COL5A2 and TGF-ß1 single nucleotide variants in pathological scarring.

Comparative Study of Carbon Nanosphere and Carbon Nanopowder on Viscosity and Thermal Conductivity of Nanofluids.

A comparative research on stability, viscosity (µ), and thermal conductivity (k) of carbon nanosphere (CNS) and carbon nanopowder (CNP) nanofluids was performed. CNS was synthesized by the hydrothermal method, while CNP was provided by the manufacturer. Stable nanofluids at high concentrations 0.5, 1.0, and 1.5 vol% were prepared successfully. The properties of CNS and CNP nanoparticles were analyzed with Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), specific surface area (SBET), X-ray powder diffraction (XRD), thermogravimetry/differential thermal analysis (TG/DTA), and energy dispersive X-ray analysis (EDX). The CNP nanofluids have the highest k enhancement of 10.61% for 1.5 vol% concentration compared to the base fluid, while the CNS does not make the thermal conductivity of nanofluids (knf) significantly higher. The studied nanofluids were Newtonian. The relative µ of CNS and CNP nanofluids was 1.04 and 1.07 at 0.5 vol% concentration and 30 °C. These results can be explained by the different sizes and crystallinity of the used nanoparticles.

An emergent neural coactivity code for dynamic memory.

Neural correlates of external variables provide potential internal codes that guide an animal's behavior. Notably, first-order features of neural activity, such as single-neuron firing rates, have been implicated in encoding information. However, the extent to which higher-order features, such as multineuron coactivity, play primary roles in encoding information or secondary roles in supporting single-neuron codes remains unclear. Here, we show that millisecond-timescale coactivity among hippocampal CA1 neurons discriminates distinct, short-lived behavioral contingencies. This contingency discrimination was unrelated to the tuning of individual neurons, but was instead an emergent property of their coactivity. Contingency-discriminating patterns were reactivated offline after learning, and their reinstatement predicted trial-by-trial memory performance. Moreover, optogenetic suppression of inputs from the upstream CA3 region during learning impaired coactivity-based contingency information in the CA1 and subsequent dynamic memory retrieval. These findings identify millisecond-timescale coactivity as a primary feature of neural firing that encodes behaviorally relevant variables and supports memory retrieval.

A Novel Experimental Study on the Rheological Properties and Thermal Conductivity of Halloysite Nanofluids.

Nanofluids obtained from halloysite and de-ionized water (DI) were prepared by using surfactants and changing pH for heat-transfer applications. The halloysite nanotubes (HNTs) nanofluids were studied for several volume fractions (0.5, 1.0, and 1.5 vol%) and temperatures (20, 30, 40, 50, and 60 °C). The properties of HNTs were studied with a scanning electron microscope (SEM), energy-dispersive X-ray analysis (EDX), Fourier-transform infrared (FT-IR) spectroscopy, X-ray powder diffraction (XRD), Raman spectroscopy and thermogravimetry/differential thermal analysis (TG/DTA). The stability of the nanofluids was proven by zeta potentials measurements and visual observation. With surfactants, the HNT nanofluids had the highest thermal conductivity increment of 18.30% for 1.5 vol% concentration in comparison with the base fluid. The thermal conductivity enhancement of nanofluids containing surfactant was slightly higher than nanofluids with pH = 12. The prepared nanofluids were Newtonian. The viscosity enhancements of the nanofluid were 11% and 12.8% at 30 °C for 0.5% volume concentration with surfactants and at pH = 12, respectively. Empirical correlations of viscosity and thermal conductivity for these nanofluids were proposed for practical applications.

Electrically Controlled Spin Injection from Giant Rashba Spin-Orbit Conductor BiTeBr.

Ferromagnetic materials are the widely used source of spin-polarized electrons in spintronic devices, which are controlled by external magnetic fields or spin-transfer torque methods. However, with increasing demand for smaller and faster spintronic components utilization of spin-orbit phenomena provides promising alternatives. New materials with unique spin textures are highly desirable since all-electric creation and control of spin polarization is expected where the strength, as well as an arbitrary orientation of the polarization, can be defined without the use of a magnetic field. In this work, we use a novel spin-orbit crystal BiTeBr for this purpose. Because of its giant Rashba spin splitting, bulk spin polarization is created at room temperature by an electric current. Integrating BiTeBr crystal into graphene-based spin valve devices, we demonstrate for the first time that it acts as a current-controlled spin injector, opening new avenues for future spintronic applications in integrated circuits.

Hydrothermal Synthesis and Gas Sensing of Monoclinic MoO3 Nanosheets.

Effects of different reaction parameters in the hydrothermal synthesis of molybdenum oxides (MoO3) were investigated and monoclinic (ß-) MoO3 was prepared hydrothermally for the first time. Various temperatures (90/210 °C, and as a novelty 240 °C) and durations (3/6 h) were used. At 240 °C, cetyltrimethylammonium bromide (CTAB) and CrCl3 additives were also tested. Both the reaction temperatures and durations played a significant role in the formation of the products. At 90 °C, h-MoO3 was obtained, while at 240 °C the orthorhombic (α-) MoO3 formed with hexagonal rod-like and nanofibrous morphology, respectively. The phase transformation between these two phases was observed at 210 °C. At this temperature, the 3 h reaction time resulted in the mixture of h- and α-MoO3, but 6 h led to pure α-MoO3. With CTAB the product was bare o-MoO3, however, when CrCl3 was applied, pure metastable m-MoO3 formed with the well-crystallized nanosheet morphology. The gas sensing of the MoO3 polymorphs was tested to H2, which was the first such gas sensing study in the case of m-WO3. Monoclinic MoO3 was found to be more sensitive in H2 sensing than o-MoO3. This initial gas sensing study indicates that m-MoO3 has promising gas sensing properties and this MoO3 polymorph is promising to be studied in detail in the future.

Effect of pH in the Hydrothermal Preparation of Bi2WO6 Nanostructures.

In this study, Bi2WO6 was prepared by the hydrothermal method. The effects of reaction temperature (150/170/200 °C) and reaction time (6/12/24 h) were investigated. The role of strongly acidic pH (1 >) and the full range between 0.3 and 13.5 were studied first. Every sample was studied by XRD and SEM; furthermore, the Bi2WO6 samples prepared at different temperatures were examined in detail by EDX and TEM, as well as FT-IR, Raman and UV-vis spectroscopies. It was found that changing the temperature and time slightly influenced the crystallinity and morphology of the products. The most crystallized product formed at 200 °C, 24 h. The pure, sheet-like Bi2WO6, prepared at 200 °C, 24 h, and 0.3 pH, gradually transformed into a mixture of Bi2WO6 and Bi3.84W0.16O6.24 with increasing pH. The nanosheets turned into a morphology of mixed shapes in the acidic range (fibers, sheets, irregular forms), and became homogenous cube- and octahedral-like shapes in the alkaline range. Their band gaps were calculated and were found to vary between 2.66 and 2.59 eV as the temperature increased. The specific surface area measurements revealed that reducing the temperature favors the formation of a larger surface area (35.8/26/21.6 m2/g belonging to 150/170/200 °C, respectively).

The influence of GSTT/GSTM null genotypes in scarring.

BACKGROUND AND AIMS: The process of scarring is a common denominator of interest for the medical field. From general medicine to dentistry, pathological scar tissue represents a challenge in providing optimal care to a patient. The present study aims to investigate whether a systemically reduced antioxidant potential, revealed by null isoforms of glutathione S transferase, affects the process of scarring in a group of female patients. METHODS: The study is based on a group of 54 patients with physiological scars after a 6-month observation period, as well as 18 patients with hypertrophic or atrophic scars. Peripheral venous blood was collected, from which DNA was extracted using a commercial kit. Genotyping followed a Multiplex PCR protocol for GSTT1/GSTM1. RESULTS: In a dominant model, the combination of wild type (heterozygous or homozygous) GSTT1 and GSTM1 was negatively associated with pathological scarring, with the wild type (heterozygous or homozygous) GSTM1 genotype being potentially responsible for this effect. Other factors affecting pathological scarring were investigated: family history, phototype, as well as scores on the POSAS and SCAR scales. CONCLUSIONS: The presence of GSTT1 and GSTM1 alleles brings forward an increased antioxidant capacity, serving as a protective factor for patients during scar formation.

Effect of Different Anions Upon the WO3 Morphology and Structure.

In this study the effects of various anions (SO2-4, ClO-4 and PO3-4) were investigated on the hydrothermal treatment of WO3 from Na2WO4 and HCl at 180 and 200 °C. The products were analyzed by XRD and SEM. With the usage of SO2-4 the obtained product was hexagonal (h-) WO3 in the form of nanorods at both temperatures. Applying ClO-4 resulted in a mixture of WO3·0.33H2O and small amount of m-WO3 at 180 °C and pure WO3·0.33H2O at 200 °C. The morphology was consisted of cuboid shapes arranged into spherical structures at 180 °C and longitudinal ones at 200 °C. By the application of PO3-4 no product formed at either temperature. Using the combination of SO2-4, and ClO-4 the product was h-WO3 at both 180 and 200 °C with rod-like crystals; thus, the effect of ClO-4 was overdominated by the SO2-4ions. Utilization of PO3-4 together with SO2-4, and/or ClO-4 resulted again in no product, meaning that adding PO3-4 to the reaction mixture completely blocks the hydrothermal formation of solid products by forming water soluble phosphotungstic acids.

Group II Metabotropic Glutamate Receptors Mediate Presynaptic Inhibition of Excitatory Transmission in Pyramidal Neurons of the Human Cerebral Cortex.

Group II metabotropic glutamate receptor (mGluR) ligands are potential novel drugs for neurological and psychiatric disorders, but little is known about the effects of these compounds at synapses of the human cerebral cortex. Investigating the effects of neuropsychiatric drugs in human brain tissue with preserved synaptic circuits might accelerate the development of more potent and selective pharmacological treatments. We have studied the effects of group II mGluR activation on excitatory synaptic transmission recorded from pyramidal neurons of cortical layers 2-3 in acute slices derived from surgically removed cortical tissue of people with epilepsy or tumors. The application of a selective group II mGluR agonist, LY354740 (0.1-1 µM) inhibited the amplitude and frequency of action potential-dependent spontaneous excitatory postsynaptic currents (sEPSCs). This effect was prevented by the application of a group II/III mGluR antagonist, CPPG (0.1 mM). Furthermore, LY354740 inhibited the frequency, but not the amplitude, of action potential-independent miniature EPSCs (mEPSCs) recorded in pyramidal neurons. Finally, LY354740 did slightly reduce cells' input resistance without altering the holding current of the neurons recorded in voltage clamp at -90 mV. Our results suggest that group II mGluRs are mainly auto-receptors that inhibit the release of glutamate onto pyramidal neurons in layers 2-3 in the human cerebral cortex, thereby regulating network excitability. We have demonstrated the effect of a group II mGluR ligand at human cortical synapses, revealing mechanisms by which these drugs could exert pro-cognitive effects and treat human neuropsychiatric disorders.

Contacting ZnO Individual Crystal Facets by Direct Write Lithography.

Many advanced electronic devices take advantage of properties developed at the surface facets of grown crystals with submicrometer dimensions. Electrical contacts to individual crystal facets can make possible the investigations of facet-dependent properties such as piezoelectricity in ZnO or III-nitride crystals having noncentrosymmetric structure. However, a lithography-based method for developing contacts to individual crystal facets with submicrometer size has not yet been demonstrated. In this report we study the use of electron beam-induced deposition (EBID), a direct write lithography method, for contacting individual facets of ZnO pillars within an electron microscope. Correlating structural and in situ deposition and electrical data, we examine proximity effects during the EBID and evaluate the process against obtaining electrically insulated contact lines on neighboring and diametrically opposite ZnO facets. Parameters such as incident beam energy geometry and size of the facets were investigated with the view of minimizing unwanted proximity broadening effects. Additionally, we show that the EBID direct write method has the required flexibility, resolution, and minimized proximity deposition for creating prototype devices. The devices were used to observe facet-dependent effects induced by mechanical stress on single ZnO pillar structures.