Features of antifungal therapy during long-lasting infectious process: a clinical case of fungal keratitis and profile of antifungal sensitivity based on assessing biofilm formation

Among infectious diseases, opportunistic mycoses hold a special place. There has been accumulating a lot of evidence regarding the clinical and epidemiological aspects of infection caused by Fusarium spp., which global incidence rate among microbial keratitis ranges from 2 to 40% depending on the geographical location of the country. Colonizing mucous membranes, fungi can exist not only in the form of plankton, but form biofilms after surface attachment, which leads to elevated resistance to multiple antifungal agents. Here we describe a clinical case of fungal keratitis due to Fusarium solani by determining profile of the antifungal sensitivity for isolated fungal strains, by taking into account their potential for biofilm formation. We used an F. solani culture isolated from the patient as well as F. solani test culture obtained from the Russian National Collection of Microorganisms. While determining the sensitivity of fungal planktonic cultures to antifungal agents from the azole group (fluconazole, voriconazole), amphotericin B and terbinafine, it was revealed that antimycotics amphotericin B and voriconazole exerted a marked antifungal activity against clinical isolate, whereas the plankton F. solani test culture was more sensitive to all groups of antifungal agents. Due to a long-lasting progressive course of the infectious process and the high biofilm-forming ability of the clinical strain F. solani, the activity of antifungal agents on biofilm cells was modeled and examined in vitro. It was shown that regarding to the fungal biofilms, value of the minimally inhibitory concentration exceeded those for planktonic cultures by 100-fold. The mechanisms of action for antifungal agents on vital parameters of fungal cell structures were analyzed by using confocal laser scanning microscopy after staining samples with propidium iodide and acridine orange for 15 min to detect changes between intact and damaged cell surface. It was found that within the biofilm fungal cells preserved viability even after exposure to high concentrations of antifungals. In addition, despite the fungicidal drug activity at substantial concentrations acting on the biofilm cell membrane, the cell nuclei remained viable. Owing to the presence ot the mechanism of resistance in mycelial fungi shown in the study, it is necessary to take into account and investigate characteristics of biofilms in terms of drug sensitivity that will allow to optimize a choice of antimicrobial therapy

Schwann cells sense and control acetylcholine spillover at the neuromuscular junction by α7 nicotinic receptors and butyrylcholinesterase

Terminal Schwann cells (TSCs) are key components of the mammalian neuromuscular junction (NMJ). How the TSCs sense the synaptic activity in physiological conditions remains unclear. We have taken advantage of the distinct localization of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at the NMJ to bring out the function of different ACh receptors (AChRs). AChE is clustered by the collagen Q in the synaptic cleft and prevents the repetitive activation of muscle nicotinic AChRs. We found that BChE is anchored at the TSC by a proline-rich membrane anchor, the small transmembrane protein anchor of brain AChE. When BChE was specifically inhibited, ACh release was significant depressed through the activation of α7 nAChRs localized on the TSC and activated by the spillover of ACh. When both AChE and BChE were inhibited, the spillover increased and induced a dramatic reduction of ACh release that compromised the muscle twitch triggered by the nerve stimulation. α7 nAChRs at the TSC may act as a sensor for spillover of ACh adjusted by BChE and may represent an extrasynaptic sensor for homeostasis at the NMJ. In myasthenic rats, selective inhibition of AChE is more effective in rescuing muscle function than the simultaneous inhibition of AChE and BChE because the concomitant inhibition of BChE counteracts the positive action of AChE inhibition. These results show that inhibition of BChE should be avoided during the treatment of myasthenia and the pharmacological reversal of residual curarization after anesthesia. © 2014 the authors

A Functional Phylogenomic View of the Seed Plants

A novel result of the current research is the development and implementation of a unique functional phylogenomic approach that explores the genomic origins of seed plant diversification. We first use 22,833 sets of orthologs from the nuclear genomes of 101 genera across land plants to reconstruct their phylogenetic relationships. One of the more salient results is the resolution of some enigmatic relationships in seed plant phylogeny, such as the placement of Gnetales as sister to the rest of the gymnosperms. In using this novel phylogenomic approach, we were also able to identify overrepresented functional gene ontology categories in genes that provide positive branch support for major nodes prompting new hypotheses for genes associated with the diversification of angiosperms. For example, RNA interference (RNAi) has played a significant role in the divergence of monocots from other angiosperms, which has experimental support in Arabidopsis and rice. This analysis also implied that the second largest subunit of RNA polymerase IV and V (NRPD2) played a prominent role in the divergence of gymnosperms. This hypothesis is supported by the lack of 24nt siRNA in conifers, the maternal control of small RNA in the seeds of flowering plants, and the emergence of double fertilization in angiosperms. Our approach takes advantage of genomic data to define orthologs, reconstruct relationships, and narrow down candidate genes involved in plant evolution within a phylogenomic view of species' diversification

Hyperon polarization along the beam direction relative to the second and third harmonic event planes in isobar collisions at sNN\sqrt{s_{NN}} = 200 GeV

The polarization of $\Lambda$ and $\bar{\Lambda}$ hyperons along the beam direction has been measured relative to the second and third harmonic event planes in isobar Ru+Ru and Zr+Zr collisions at $\sqrt{s_{NN}}$ = 200 GeV. This is the first experimental evidence of the hyperon polarization by the triangular flow originating from the initial density fluctuations. The amplitudes of the sine modulation for the second and third harmonic results are comparable in magnitude, increase from central to peripheral collisions, and show a mild $p_T$ dependence. The azimuthal angle dependence of the polarization follows the vorticity pattern expected due to elliptic and triangular anisotropic flow, and qualitatively disagree with most hydrodynamic model calculations based on thermal vorticity and shear induced contributions. The model results based on one of existing implementations of the shear contribution lead to a correct azimuthal angle dependence, but predict centrality and $p_T$ dependence that still disagree with experimental measurements. Thus, our results provide stringent constraints on the thermal vorticity and shear-induced contributions to hyperon polarization. Comparison to previous measurements at RHIC and the LHC for the second-order harmonic results shows little dependence on the collision system size and collision energy.Comment: 6 pages, 5 figures, Published in Physical Review Letter

Observation of the electromagnetic field effect via charge-dependent directed flow in heavy-ion collisions at the Relativistic Heavy Ion Collider

The deconfined quark-gluon plasma (QGP) created in relativistic heavy-ion collisions enables the exploration of the fundamental properties of matter under extreme conditions. Non-central collisions can produce strong magnetic fields on the order of $10^{18}$ Gauss, which offers a probe into the electrical conductivity of the QGP. In particular, quarks and anti-quarks carry opposite charges and receive contrary electromagnetic forces that alter their momenta. This phenomenon can be manifested in the collective motion of final-state particles, specifically in the rapidity-odd directed flow, denoted as $v_1(\mathsf{y})$. Here we present the charge-dependent measurements of $dv_1/d\mathsf{y}$ near midrapidities for $\pi^{\pm}$, $K^{\pm}$, and $p(\bar{p})$ in Au+Au and isobar ($_{44}^{96}$Ru+$_{44}^{96}$Ru and $_{40}^{96}$Zr+$_{40}^{96}$Zr) collisions at $\sqrt{s_{\rm NN}}=$ 200 GeV, and in Au+Au collisions at 27 GeV, recorded by the STAR detector at the Relativistic Heavy Ion Collider. The combined dependence of the $v_1$ signal on collision system, particle species, and collision centrality can be qualitatively and semi-quantitatively understood as several effects on constituent quarks. While the results in central events can be explained by the $u$ and $d$ quarks transported from initial-state nuclei, those in peripheral events reveal the impacts of the electromagnetic field on the QGP. Our data put valuable constraints on the electrical conductivity of the QGP in theoretical calculations

Event-by-event correlations between Λ\Lambda (Λˉ\bar{\Lambda}) hyperon global polarization and handedness with charged hadron azimuthal separation in Au+Au collisions at sNN=27 GeV\sqrt{s_{\text{NN}}} = 27 \text{ GeV} from STAR

Global polarizations ($P$) of $\Lambda$ ($\bar{\Lambda}$) hyperons have been observed in non-central heavy-ion collisions. The strong magnetic field primarily created by the spectator protons in such collisions would split the $\Lambda$ and $\bar{\Lambda}$ global polarizations ($\Delta P = P_{\Lambda} - P_{\bar{\Lambda}} < 0$). Additionally, quantum chromodynamics (QCD) predicts topological charge fluctuations in vacuum, resulting in a chirality imbalance or parity violation in a local domain. This would give rise to an imbalance ($\Delta n = \frac{N_{\text{L}} - N_{\text{R}}}{\langle N_{\text{L}} + N_{\text{R}} \rangle} \neq 0$) between left- and right-handed $\Lambda$ ($\bar{\Lambda}$) as well as a charge separation along the magnetic field, referred to as the chiral magnetic effect (CME). This charge separation can be characterized by the parity-even azimuthal correlator ($\Delta\gamma$) and parity-odd azimuthal harmonic observable ($\Delta a_{1}$). Measurements of $\Delta P$, $\Delta\gamma$, and $\Delta a_{1}$ have not led to definitive conclusions concerning the CME or the magnetic field, and $\Delta n$ has not been measured previously. Correlations among these observables may reveal new insights. This paper reports measurements of correlation between $\Delta n$ and $\Delta a_{1}$, which is sensitive to chirality fluctuations, and correlation between $\Delta P$ and $\Delta\gamma$ sensitive to magnetic field in Au+Au collisions at 27 GeV. For both measurements, no correlations have been observed beyond statistical fluctuations.Comment: 10 pages, 10 figures; paper from the STAR Collaboratio

Tomography of Ultra-relativistic Nuclei with Polarized Photon-gluon Collisions

A linearly polarized photon can be quantized from the Lorentz-boosted electromagnetic field of a nucleus traveling at ultra-relativistic speed. When two relativistic heavy nuclei pass one another at a distance of a few nuclear radii, the photon from one nucleus may interact through a virtual quark-antiquark pair with gluons from the other nucleus forming a short-lived vector meson (e.g. ${\rho^0}$). In this experiment, the polarization was utilized in diffractive photoproduction to observe a unique spin interference pattern in the angular distribution of ${\rho^0\rightarrow\pi^+\pi^-}$ decays. The observed interference is a result of an overlap of two wave functions at a distance an order of magnitude larger than the ${\rho^0}$ travel distance within its lifetime. The strong-interaction nuclear radii were extracted from these diffractive interactions, and found to be $6.53\pm 0.06$ fm ($^{197} {\rm Au }$) and $7.29\pm 0.08$ fm ($^{238} {\rm U}$), larger than the nuclear charge radii. The observable is demonstrated to be sensitive to the nuclear geometry and quantum interference of non-identical particles

Observation of Global Spin Alignment of ϕ\phi and K∗0K^{*0} Vector Mesons in Nuclear Collisions

The strong force, as one of the four fundamental forces at work in the universe, governs interactions of quarks and gluons, and binds together the atomic nucleus. Notwithstanding decades of progress since Yukawa first developed a description of the force between nucleons in terms of meson exchange, a full understanding of the strong interaction remains a major challenge in modern science. One remaining difficulty arises from the non-perturbative nature of the strong force, which leads to the phenomenon of quark confinement at distance scales on the order of the size of the proton. Here we show that in relativistic heavy-ion collisions, where quarks and gluons are set free over an extended volume, two species of produced vector (spin-1) mesons, namely $\phi$ and $K^{*0}$, emerge with a surprising pattern of global spin alignment. In particular, the global spin alignment for $\phi$ is unexpectedly large, while that for $K^{*0}$ is consistent with zero. The observed spin-alignment pattern and magnitude for the $\phi$ cannot be explained by conventional mechanisms, while a model with strong force fields accommodates the current data. This is the first time that the strong force field is experimentally supported as a key mechanism that leads to global spin alignment. We extract a quantity proportional to the intensity of the field of the strong force. Within the framework of the Standard Model, where the strong force is typically described in the quark and gluon language of Quantum Chromodynamics, the field being considered here is an effective proxy description. This is a qualitatively new class of measurement, which opens a new avenue for studying the behaviour of strong force fields via their imprint on spin alignment

Schwann cells sense and control acetylcholine spillover at the neuromuscular junction by α7 nicotinic receptors and butyrylcholinesterase

Terminal Schwann cells (TSCs) are key components of the mammalian neuromuscular junction (NMJ). How the TSCs sense the synaptic activity in physiological conditions remains unclear. We have taken advantage of the distinct localization of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at the NMJ to bring out the function of different ACh receptors (AChRs). AChE is clustered by the collagen Q in the synaptic cleft and prevents the repetitive activation of muscle nicotinic AChRs. We found that BChE is anchored at the TSC by a proline-rich membrane anchor, the small transmembrane protein anchor of brain AChE. When BChE was specifically inhibited, ACh release was significant depressed through the activation of α7 nAChRs localized on the TSC and activated by the spillover of ACh. When both AChE and BChE were inhibited, the spillover increased and induced a dramatic reduction of ACh release that compromised the muscle twitch triggered by the nerve stimulation. α7 nAChRs at the TSC may act as a sensor for spillover of ACh adjusted by BChE and may represent an extrasynaptic sensor for homeostasis at the NMJ. In myasthenic rats, selective inhibition of AChE is more effective in rescuing muscle function than the simultaneous inhibition of AChE and BChE because the concomitant inhibition of BChE counteracts the positive action of AChE inhibition. These results show that inhibition of BChE should be avoided during the treatment of myasthenia and the pharmacological reversal of residual curarization after anesthesia. © 2014 the authors

Board of Trustees Meeting, July 19, 1976

The agendas for meetings of the Johnson County Community College Board of Trustee