The molecular genetic regulation of vegetative-generative transition in wheat from environmental perspective.

The key to wide geographical distribution of wheat is its high adaptability. One of the most commonly used methods for studying adaptation is the investigation of transition between the vegetative-generative phase and the subsequent intensive stem elongation process. These processes are largely determined by changes in ambient temperature, the diurnal and annual periodicity of day length, and the composition of light spectrum.

Novel multitarget analgesic candidate SZV-1287 demonstrates potential disease-modifying effects in the monoiodoacetate-induced osteoarthritis mouse model.

Introduction: Monoiodoacetate (MIA)-induced osteoarthritis (OA) is the most commonly used rodent model for testing anti-OA drug candidates. Herein, we investigated the effects of our patented multitarget drug candidate SZV-1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl) propanal oxime) that is currently under clinical development for neuropathic pain and characterized the mouse model through complex functional, imaging, and morphological techniques.

Methods: Knee OA was induced by intraarticular MIA injection (0.

Phthalazine as a Diene in Diels-Alder Reactions With P- and As-Containing Anionic Dienophiles: Comparison of Possible Reaction Channels.

Phthalazine can behave as a diene in Diels-Alder (DA) cycloadditions, typically at the pyridazine ring, however, its application is somewhat limited because these reactions usually require harsh conditions or sophisticated catalysts. As an unconventional example, phthalazine was reported to undergo cycloaddition with the [PCO] anion without any catalyst. In this computational study, we scrutinise the mechanism of the DA reactions between phthalazine and the so far known [ECX] (E: P, As; X: O, S, Se) anions as dienophiles.

Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model.

The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involving acute pain models in mice.

Assessing the Impact of Influenza Vaccination Timing on Experimental Arthritis: Effects on Disease Progression and Inflammatory Biomarkers.

Numerous studies have indicated a link between vaccines and the exacerbation of autoimmune diseases including rheumatoid arthritis (RA). However, there is no consensus in clinical practice regarding the optimal timing of immunization. Therefore, this study aimed to investigate the impact of the 3Fluart influenza vaccine on the complete Freund's adjuvant (CFA)-induced chronic arthritis rat model and to identify new biomarkers with clinical utility.

The Epigenetics of Neuropathic Pain: A Systematic Update.

Epigenetics deals with alterations to the gene expression that occur without change in the nucleotide sequence in the DNA. Various covalent modifications of the DNA and/or the surrounding histone proteins have been revealed, including DNA methylation, histone acetylation, and methylation, which can either stimulate or inhibit protein expression at the transcriptional level. In the past decade, an exponentially increasing amount of data has been published on the association between epigenetic changes and the pathomechanism of pain, including its most challenging form, neuropathic pain.

Strategic use of observer-perspective questions in couples therapy.

Questions are one of the most frequently used strategies in therapy. There is a body of theoretical work on the kinds of questions that are preferred in specific treatment approaches. However, research on the use of questions in general, how they are formed and what specific therapeutic work they do, is relatively scarce in the literature.

Lacking ARHGAP25 mitigates the symptoms of autoantibody-induced arthritis in mice.

Objective: Despite intensive research on rheumatoid arthritis, the pathomechanism of the disease is still not fully understood and the treatment has not been completely resolved. Previously we demonstrated that the GTPase-activating protein, ARHGAP25 has a crucial role in the regulation of basic phagocyte functions. Here we investigate the role of ARHGAP25 in the complex inflammatory process of autoantibody-induced arthritis.

Myeloid Src-family kinases are critical for neutrophil-mediated autoinflammation in gout and motheaten models.

Autoinflammatory diseases include a number of monogenic systemic inflammatory diseases, as well as acquired autoinflammatory diseases such as gout. Here, we show that the myeloid Src-family kinases Hck, Fgr, and Lyn are critical for experimental models of gout, as well as for genetically determined systemic inflammation in the Ptpn6me-v/me-v (motheaten viable) mouse model. The Hck-/-Fgr-/-Lyn-/- mutation abrogated various monosodium urate (MSU) crystal-induced pro-inflammatory responses of neutrophils, and protected mice from the development of gouty arthritis.

Effects of genetic components of plant development on yield-related traits in wheat ( L.) under stress-free conditions.

The dynamics of plant development not only has an impact on ecological adaptation but also contributes to the realization of genetically determined yield potentials in various environments. Dissecting the genetic determinants of plant development becomes urgent due to the global climate change, which can seriously affect and even disrupt the locally adapted developmental patterns. In order to determine the role plant developmental loci played in local adaptation and yield formation, a panel of 188 winter and facultative wheat cultivars from diverse geographic locations were characterized with the 15K Illumina Single Nucleotide Polymorphism (SNP) chip and functional markers of several plant developmental genes and included into a multiseason field experiment.

The heptapeptide somatostatin analogue TT-232 exerts analgesic and anti-inflammatory actions via SST receptor activation: In silico, in vitro and in vivo evidence in mice.

Since the conventional and adjuvant analgesics have limited effectiveness frequently accompanied by serious side effects, development of novel, potent pain killers for chronic neuropathic and inflammatory pain conditions is a big challenge. Somatostatin (SS) regulates endocrine, vascular, immune and neuronal functions, cell proliferation through 5 G protein-coupled receptors (SST-SST). SS released from the capsaicin-sensitive peptidergic sensory nerves mediates anti-inflammatory and antinociceptive effects without endocrine actions via SST.

Effect of Lipid Raft Disruptors on Cell Membrane Fluidity Studied by Fluorescence Spectroscopy.

Lipid rafts are specialized microdomains in cell membranes, rich in cholesterol and sphingolipids, and play an integrative role in several physiological and pathophysiological processes. The integrity of rafts can be disrupted via their cholesterol content-with methyl-β-cyclodextrin (MCD) or with our own carboxamido-steroid compound (C1)-or via their sphingolipid content-with sphingomyelinase (SMase) or with myriocin (Myr). We previously proved by the fluorescent spectroscopy method with LAURDAN that treatment with lipid raft disruptors led to a change in cell membrane polarity.

Effect of additional water supply during grain filling on protein composition and epitope characteristics of winter oats.

Pure oats in gluten-free diets (GFD) represent important nutritional benefits for people suffering from celiac disease (CD). However, oat cultivars do not contain the typical CD-related wheat gliadin analog polypeptides. Emerging evidence suggests that oat cultivars containing gluten-like epitopes in avenin sequences may pose potential health risks for celiac patients in rare cases, depending on the individual's susceptibility.

Understanding the Mechanism of Diels-Alder Reactions with Anionic Dienophiles: A Systematic Comparison of [ECX] (E = P, As; X = O, S, Se) Anions.

While Diels-Alder (DA) reactions involving neutral or cationic dienophiles are well-known, the characteristics of the analogous reactions with anionic dienophiles are practically unexplored. Herein we present the first comparative computational investigations on the characteristics of DA cycloadditions with anionic dienophiles on the basis of the reactions of [ECX] anions (E = P, As; X = O, S, Se) with 2-pyran-2-one. All of these reactions were found to be both kinetically and thermodynamically feasible, enabling synthetic access toward 2-phosphaphenolate and arsaphenolate derivatives in the future.

Experimental Arthritis Inhibits Adult Hippocampal Neurogenesis in Mice.

Adult-born neurons of the hippocampal dentate gyrus play a role in specific forms of learning, and disturbed neurogenesis seems to contribute to the development of neuropsychiatric disorders, such as major depression. Neuroinflammation inhibits adult neurogenesis, but the effect of peripheral inflammation on this form of neuroplasticity is ambiguous. : Our aim was to investigate the influence of acute and chronic experimental arthritis on adult hippocampal neurogenesis and to elucidate putative regulatory mechanisms.

Exploring the legacy of Central European historical winter wheat landraces.

Historical wheat landraces are rich sources of genetic diversity offering untapped reservoirs for broadening the genetic base of modern varieties. Using a 20K SNP array, we investigated the accessible genetic diversity in a Central European bread wheat landrace collection with great drought, heat stress tolerance and higher tillering capacity. We discovered distinct differences in the number of average polymorphisms between landraces and modern wheat cultivars, and identified a set of novel rare alleles present at low frequencies in the landrace collection.

Phospholipase Cγ2 Is Essential for Experimental Models of Epidermolysis Bullosa Acquisita.

Phospholipase Cγ2 (PLCγ2) mediates tyrosine kinase‒coupled receptor signaling in various hematopoietic lineages. Although PLCγ2 has been implicated in certain human and mouse inflammatory disorders, its contribution to autoimmune and inflammatory skin diseases is poorly understood. In this study, we tested the role of PLCγ2 in a mouse model of epidermolysis bullosa acquisita triggered by antibodies against type VII collagen (C7), a component of the dermo-epidermal junction.

Proof-of-Concept for the Analgesic Effect and Thermoregulatory Safety of Orally Administered Multi-Target Compound SZV 1287 in Mice: A Novel Drug Candidate for Neuropathic Pain.

SZV 1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime) is a novel multi-target candidate under preclinical development for neuropathic pain. It inhibits amine oxidase copper containing 3, transient receptor potential ankyrin 1 and vanilloid 1 (TRPV1) receptors. Mainly under acidic conditions, it is transformed to the cyclooxygenase inhibitor oxaprozin, which is ineffective for neuropathy.

The evolution of patients' concept of the alliance and its relation to outcome: A dynamic latent-class structural equation modeling approach.

The working alliance (WA) has been widely identified as the key concept for psychotherapy and allied health care services. The WA, measured at different phases of diverse kinds of therapies, has been shown to robustly predict posttreatment outcomes. But the way the clients' conceptualization of the alliance evolves overtime, and the relation between this kind of conceptual change and subsequent symptom improvements, has not been investigated.

Single versus repeated heat stress in wheat: What are the consequences in different developmental phases?

With a possible reference to heat priming and to characterize the extent and variation in the heat stress responses in wheat, the effects of single vs. repeated heat stresses were examined by measuring the changes in morphological and grain yield-related traits and photosynthetic parameters. To achieve these objectives, 51 winter wheat cultivars of various geographic origins were included in two independent experiments covering different phenological stages.

Examining therapist effects in the alliance-outcome relationship: A multilevel meta-analysis.

Objective: The relationship between the therapeutic alliance and outcome has been supported consistently over time. More recently, studies have examined therapist effects in the alliance-outcome relationship and came up with somewhat mixed findings. The purpose of this study was to replicate and extend previous meta-analytic work using a much larger data set, permitting not only the verification of the overall impact of the therapists' contribution but, at the same time, controlling for several potential covariates effecting this relationship.

, and Pharmacodynamic Characterization of Novel Analgesic Drug Candidate Somatostatin SST Receptor Agonists.

Somatostatin released from the capsaicin-sensitive sensory nerves mediates analgesic and anti-inflammatory effects via its receptor subtype 4 (SST) without influencing endocrine functions. Therefore, SST is considered to be a novel target for drug development in pain, especially chronic neuropathy which is a great unmet medical need. Here, we examined the binding, SST-linked G protein activation and β-arrestin activation on stable SST expressing cells and the effects of our novel pyrrolo-pyrimidine molecules (20, 100, 500, 1,000, 2,000 µg·kg) on partial sciatic nerve ligation-induced traumatic mononeuropathic pain model in mice.

Analgesic Effects of Lipid Raft Disruption by Sphingomyelinase and Myriocin via Transient Receptor Potential Vanilloid 1 and Transient Receptor Potential Ankyrin 1 Ion Channel Modulation.

Transient Receptor Potential (TRP) Vanilloid 1 and Ankyrin 1 (TRPV1, TRPA1) cation channels are expressed in nociceptive primary sensory neurons, and integratively regulate nociceptor and inflammatory functions. Lipid rafts are liquid-ordered plasma membrane microdomains rich in cholesterol, sphingomyelin and gangliosides. We earlier showed that lipid raft disruption inhibits TRPV1 and TRPA1 functions in primary sensory neuronal cultures.