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Cholinergic polymodal chemosensory cells in the mammalian urethra (urethral brush cells = UBC) functionally express the canonical bitter and umami taste transduction signaling cascade. Here, we aimed to determine whether UBC are functionally equipped for the perception of salt through ENaC (epithelial sodium channel). Cholinergic UBC were isolated from ChAT-eGFP reporter mice (ChAT = choline acetyltransferase). RT-PCR showed mRNA expression of ENaC subunits Scnn1a, Scnn1b, and Scnn1g in urethral epithelium and isolated UBC. Scnn1a could also be detected by next generation sequencing in 4/6 (66%) single UBC, two of them also expressed the bitter receptor Tas2R108. Strong expression of Scnn1a was seen in some urothelial umbrella cells and in 65% of UBC (30/46 cells) in a Scnn1a reporter mouse strain. Intracellular [Ca2+] was recorded in isolated UBC stimulated with the bitter substance denatonium benzoate (25 mM), ATP (0.5 mM) and NaCl (50 mM, on top of 145 mM Na+ and 153 mM Cl- baseline in buffer); mannitol (150 mM) served as osmolarity control. NaCl, but not mannitol, evoked an increase in intracellular [Ca2+] in 70% of the tested UBC. The NaCl-induced effect was blocked by the ENaC inhibitor amiloride (IC50 = 0.471 mu M). When responses to both NaCl and denatonium were tested, all three possible positive response patterns occurred in a balanced distribution: 42% NaCl only, 33% denatonium only, 25% to both stimuli. A similar reaction pattern was observed with ATP and NaCl as test stimuli. About 22% of the UBC reacted to all three stimuli. Thus, NaCl evokes calcium responses in several UBC, likely involving an amiloride-sensitive channel containing alpha-ENaC. This feature does not define a new subpopulation of UBC, but rather emphasizes their polymodal character. The actual function of alpha-ENaC in cholinergic UBC-salt perception, homeostatic ion transport, mechanoreception-remains to be determined.
Evolutionary conservation of the antimicrobial function of mucus: a first defence against infection
(2018)
Mucus layers often provide a unique and multi-functional hydrogel interface between the epithelial cells of organisms and their external environment. Mucus has exceptional properties including elasticity, changeable rheology and an ability to self-repair by reannealing, and is therefore an ideal medium for trapping and immobilising pathogens and serving as a barrier to microbial infection. The ability to produce a functional surface mucosa was an important evolutionary step, which evolved first in the Cnidaria, which includes corals, and the Ctenophora. This allowed the exclusion of non-commensal microbes and the subsequent development of the mucus-lined digestive cavity seen in higher metazoans. The fundamental architecture of the constituent glycoprotein mucins is also evolutionarily conserved. Although an understanding of the biochemical interactions between bacteria and the mucus layer are important to the goal of developing new antimicrobial strategies, they remain relatively poorly understood. This review summarises the physicochemical properties and evolutionary importance of mucus, which make it so successful in the prevention of bacterial infection. In addition, the strategies developed by bacteria to counteract the mucus layer are also explored.
The epithelial sodium channel (ENaC) is a critical regulator of vertebrate electrolyte homeostasis. ENaC is the only constitutively open ion channel in the degenerin/ENaC protein family, and its expression, membrane abundance, and open probability therefore are tightly controlled. The canonical ENaC is composed of three subunits (, , and ), but a fourth -subunit may replace and form atypical -ENaCs. Using Xenopus laevis as a model, here we found that mRNAs of the - and -subunits are differentially expressed in different tissues and that -ENaC predominantly is present in the urogenital tract. Using whole-cell and single-channel electrophysiology of oocytes expressing Xenopus - or -ENaC, we demonstrate that the presence of the -subunit enhances the amount of current generated by ENaC due to an increased open probability, but also changes current into a transient form. Activity of canonical ENaCs is critically dependent on proteolytic processing of the - and -subunits, and immunoblotting with epitope-tagged ENaC subunits indicated that, unlike -ENaC, the -subunit does not undergo proteolytic maturation by the endogenous protease furin. Furthermore, currents generated by -ENaC were insensitive to activation by extracellular chymotrypsin, and presence of the -subunit prevented cleavage of -ENaC at the cell surface. Our findings suggest that subunit composition constitutes an additional level of ENaC regulation, and we propose that the Xenopus -ENaC subunit represents a functional example that demonstrates the importance of proteolytic maturation during ENaC evolution.
One of the main aims of current social robotic research is to improve the robots’ abilities to interact with humans. In order to achieve an interaction similar to that among humans, robots should be able to communicate in an intuitive and natural way and appropriately interpret human affects during social interactions. Similarly to how humans are able to recognize emotions in other humans, machines are capable of extracting information from the various ways humans convey emotions-including facial expression, speech, gesture or text-and using this information for improved human computer interaction. This can be described as Affective Computing, an interdisciplinary field that expands into otherwise unrelated fields like psychology and cognitive science and involves the research and development of systems that can recognize and interpret human affects. To leverage these emotional capabilities by embedding them in humanoid robots is the foundation of the concept Affective Robots, which has the objective of making robots capable of sensing the user’s current mood and personality traits and adapt their behavior in the most appropriate manner based on that. In this paper, the emotion recognition capabilities of the humanoid robot Pepper are experimentally explored, based on the facial expressions for the so-called basic emotions, as well as how it performs in contrast to other state-of-the-art approaches with both expression databases compiled in academic environments and real subjects showing posed expressions as well as spontaneous emotional reactions. The experiments’ results show that the detection accuracy amongst the evaluated approaches differs substantially. The introduced experiments offer a general structure and approach for conducting such experimental evaluations. The paper further suggests that the most meaningful results are obtained by conducting experiments with real subjects expressing the emotions as spontaneous reactions.
Through the “Act to Strengthen the Non-financial Reporting by Corporations in their Management and Group Management Reports” (Gesetz zur Stärkung der nichtfinanziellen Berichterstattung der Unternehmen in ihren Lage- und Konzernlageberichten) (CSR Directive Transposition Act, „CSR-RUG“) of 11 April 2017[1], the German Bundestag implemented Directive 2014/95/EU (“CSR Directive”)[2] into German law. Following the European impetus, the CSR-RUG enriches the traditional repertoire of forms of action under environmental law by a further instrument. Already the regulatory context gives an idea of its atypical nature: The centrepiece of the CSR-RUG is the amendment of and addition to the Third Book of the German Commercial Code (Handelsgesetzbuch, “HGB”), which deals with the “trading books” of undertakings, i.e., accounting and reporting requirements. Since the reporting year 2017, large capital market-oriented corporations must report extensively within the framework of their annual management reports on their activities and effects in certain areas of “Corporate Social Responsibility”. This also includes environmental matters. The transparency and publicity this entails is intended to generate positive stimuli for more responsible, sustained and not least of all environmentally friendly entrepreneurial action.
Following a brief presentation of the European legal bases and their implementation in Germany (I.), we will classify the provisions within the underlying concept of Corporate Social Responsibility (II.) and analyse and systemise the governance effects of non-financial reporting (III.). A few remarks on selected aspects of the chosen approach and its implementation (IV.) as well as an outlook summarising our conclusions (V.) will complete this article. By detailing the German approach to transposing the CSR Directive, this paper intends to provide an example of the challenges member state legislators face when complying with modern governance concepts such as Corporate Social Responsibility by way of non-financial reporting obligations.
[1] Federal Law Gazette, Part I 2017, 802 et seq.
[2] Directive 2014/95/EU of the European Parliament and of the Council 22 October 2014 amending Directive 2013/34/EU as regards disclosure of non-financial and diversity information by certain large undertakings and groups, OJ EU No. L 330, p. 1.
Further development on globally convergent algorithms for solution of stationary network problems is presented. The algorithms make use of global non-degeneracy of Jacobi matrix of the system, composed of Kirchhoff's flow conservation conditions and transport element equations. This property is achieved under certain monotonicity conditions on element equations and guarantees an existence of a unique solution of the problem as well as convergence to this solution from an arbitrary starting point. In application to gas transport networks, these algorithms are supported by a proper modeling of gas compressors, based on individually calibrated physical characteristics. This paper extends the modeling of compressors by hierarchical methods of topological reduction, combining the working diagrams for parallel and sequential connections of compressors. Estimations are also made for application of topological reduction methods beyond the compressor stations in generic network problems. Efficiency of the methods is tested by numerical experiments on realistic networks.
Pozzolanic properties of Pennisetum purpureum grass ash were tested on Portland cement. Results show that the ash can be blended with cements without compromising binding strength of the cement. It was found that Portland cement could be blended with Pennisetum purpureum up to a ratio of 3:2 compromising compressive strength of mortar.Mortar with lower cement replacement took longer to set as evidenced by lower compressive strength within the 28-day aging time. Mortar with higher cement replacement had lower water absorption capacity, an indication that the test pozzolan was of smaller particulate size. XRF analysis and the FTIR spectrum showed that the ash has a higher content of silica. The XRD pattern of the ash showed that the ash was predominantly amorphous. SEM images showed that the ash produced at 600 o C had residual carbon material.
New approaches in securing more sustainable urban food futures: case from Cologne-Bonn region
(2018)
Maintaining orientation in an environment with non-Earth gravity (1 g) is critical for an astronaut's operational performance. Such environments present a number of complexities for balance and motion. For example, when an astronaut tilts due to ascending or descending an inclined plane on the moon, the gravity vector will be tilted correctly, but the magnitude will be different from on earth. If this results in a mis-perceived tilt, then that may lead to postural and perceptual errors, such as mis-perceiving the orientation of oneself or the ground plane and corresponding errors in task judgment.
We present the performance of the upGREAT heterodyne array receivers on the SOFIA telescope after several years of operations. This instrument is a multi-pixel high resolution (R≳107) spectrometer for the Stratospheric Observatory for Far-Infrared Astronomy (SOFIA). The receivers use 7-pixel subarrays configured in a hexagonal layout around a central pixel. The low frequency array receiver (LFA) has 2×7 pixels (dual polarization), and presently covers the 1.83–2.07THz frequency range, which allows to observe the [CII] and [OI] lines at 158μm and 145μm wavelengths. The high frequency array (HFA) covers the [OI] line at 63μm and is equipped with one polarization at the moment (7 pixels, which can be upgraded in the near future with a second polarization array). The 4.7THz array has successfully flown using two separate quantum-cascade laser local oscillators from two different groups. NASA completed the development, integration and testing of a dual-channel closed-cycle cryocooler system, with two independently operable He compressors, aboard SOFIA in early 2017 and since then, both arrays can be operated in parallel using a frequency separating dichroic mirror. This configuration is now the prime GREAT configuration and has been added to SOFIA’s instrument suite since observing cycle 6.
Polyurethane (PU) coatings were successfully produced using unmodified kraft lignin (KL) as an environmentally benign component in contents of up to 80 wt%. Lignin samples were precipitated from industrial black liquor in aqueous solution working at room temperature and different pH levels (pH 2 to pH 5). Lignins were characterized by UV-Vis, FTIR, pyrolysis-GC/MS, SEC and 31P-NMR. Results show a correlation between pH level, OH number and molecular weight Mw of isolated lignins. Lignin-based polyurethane coatings were prepared in an efficient one step synthesis dissolving lignin in THF and PEG425 in an ultrasonic bath followed by addition of 4,4-diphenylmethanediisocyanate (MDI) and triethylamine (TEA). Crosslinking was achieved under very mild conditions (1 hour at room temperature followed by 3 hours at 35 °C). The resulting coatings were characterized regarding their physical properties including ATR-IR, TGA, optical contact angle, light microscopy, REM-EDX and AFM data. Transparent homogeneous films of high flexibility resulted from lignins isolated at pH 4, possessing a temperature resistance up to 160 °C. Swelling tests revealed a resistance against water. Swelling in DMSO depends on index, pH of precipitation and catalyst utilization for PU preparation. According to AFM studies, surface roughness is between 10 and 28 nm.
Small Molecules Enhance Scaffold-Based Bone Grafts via Purinergic Receptor Signaling in Stem Cells
(2018)
The need for bone grafts is high, due to age-related diseases, such as tumor resections, but also accidents, risky sports, and military conflicts. The gold standard for bone grafting is the use of autografts from the iliac crest, but the limited amount of accessible material demands new sources of bone replacement. The use of mesenchymal stem cells or their descendant cells, namely osteoblast, the bone-building cells and endothelial cells for angiogenesis, combined with artificial scaffolds, is a new approach. Mesenchymal stem cells (MSCs) can be obtained from the patient themselves, or from donors, as they barely cause an immune response in the recipient. However, MSCs never fully differentiate in vitro which might lead to unwanted effects in vivo. Interestingly, purinergic receptors can positively influence the differentiation of both osteoblasts and endothelial cells, using specific artificial ligands. An overview is given on purinergic receptor signaling in the most-needed cell types involved in bone metabolism-namely osteoblasts, osteoclasts, and endothelial cells. Furthermore, different types of scaffolds and their production methods will be elucidated. Finally, recent patents on scaffold materials, as wells as purinergic receptor-influencing molecules which might impact bone grafting, are discussed.
Argentina substantially contributes to the global organic agriculture and food sector due to its large areas of organically managed agricultural land. However, most of the organic production is intended for export. Overall, food supply for the domestic organic market is hardly tapped. Based on this, we investigate the current importance of organic agriculture and food production as well as consumption attitudes and behavior within the country. The novelty of the study also lies in the observation, documentation and analysis of latest stakeholder‐driven developments towards organic agriculture and food. Furthermore, the publication allows the Argentinean organic market to be significantly more visible for the international audience.
Antioxidant activity is an essential aspect of oxygen-sensitive merchandise and goods, such as food and corresponding packaging, cosmetics, and biomedicine. Technical lignin has not yet been applied as a natural antioxidant, mainly due to the complex heterogeneous structure and polydispersity of lignin. This report presents antioxidant capacity studies completed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The influence of purification on lignin structure and activity was investigated. The purification procedure showed that double-fold selective extraction is the most efficient (confirmed by ultraviolet-visible (UV/Vis), Fourier transform infrared (FTIR), heteronuclear single quantum coherence (HSQC) and 31P nuclear magnetic resonance spectroscopy, size exclusion chromatography, and X-ray diffraction), resulting in fractions of very narrow polydispersity (3.2⁻1.6), up to four distinct absorption bands in UV/Vis spectroscopy. Due to differential scanning calorimetry measurements, the glass transition temperature increased from 123 to 185 °C for the purest fraction. Antioxidant capacity is discussed regarding the biomass source, pulping process, and degree of purification. Lignin obtained from industrial black liquor are compared with beech wood samples: antioxidant activity (DPPH inhibition) of kraft lignin fractions were 62⁻68%, whereas beech and spruce/pine-mixed lignin showed values of 42% and 64%, respectively. Total phenol content (TPC) of the isolated kraft lignin fractions varied between 26 and 35%, whereas beech and spruce/pine lignin were 33% and 34%, respectively. Storage decreased the TPC values but increased the DPPH inhibition.
Serine/threonine kinase 4 (STK4) deficiency is an autosomal recessive genetic condition that leads to primary immunodeficiency (PID) typically characterized by lymphopenia, recurrent infections and Epstein Barr Virus (EBV) induced lymphoproliferation and -lymphoma. State-of-the-art treatment regimens consist of prevention or treatment of infections, immunoglobulin substitution (IVIG) and restoration of the immune system by hematopoietic stem cell transplantation. Here, we report on two patients from two consanguineous families of Turkish (patient P1) and Moroccan (patient P2) decent, with PID due to homozygous STK4 mutations. P1 harbored a previously reported frameshift (c.1103 delT, p.M368RfsX2) and P2 a novel splice donor site mutation (P2; c.525+2 T>G). Both patients presented in childhood with recurrent infections, CD4 lymphopenia and dysregulated immunoglobulin levels. Patient P1 developed a highly malignant B cell lymphoma at the age of 10 years and a second, independent Hodgkin lymphoma 5 years later. To our knowledge she is the first STK4 deficient case reported who developed lymphoma in the absence of detectable EBV or other common viruses. Lymphoma development may be due to the lacking tumor suppressive function of STK4 or the perturbed immune surveillance due to the lack of CD4+ T cells. Our data should raise physicians' awareness of [1] lymphoma proneness of STK4 deficient patients even in the absence of EBV infection and [2] possibly underlying STK4 deficiency in pediatric patients with a history of recurrent infections, CD4 lymphopenia and lymphoma and unknown genetic make-up. Patient P2 experienced recurrent otitis in childhood, but when she presented at the age of 14, she showed clinical and immunological characteristics similar to patients suffering from Autoimmune Lymphoproliferative Syndrome (ALPS): elevated DNT cell number, non-malignant lymphadenopathy and hepatosplenomegaly, hematolytic anemia, hypergammaglobulinemia. Also patient P1 presented with ALPS-like features (lymphadenopathy, elevated DNT cell number and increased Vitamin B12 levels) and both were initially clinically diagnosed as ALPS-like. Closer examination of P2, however, revealed active EBV infection and genetic testing identified a novel STK4 mutation. None of the patients harbored typically ALPS-associated mutations of the Fas receptor mediated apoptotic pathway and Fas-mediated apoptosis was not affected. The presented case reports extend the clinical spectrum of STK4 deficiency.
Females are influenced more than males by visual cues during many spatial orientation tasks; but females rely more heavily on gravitational cues during visual-vestibular conflict. Are there gender biases in the relative contributions of vision, gravity and the internal representation of the body to the perception of upright? And might any such biases be affected by low gravity? 16 participants (8 female) viewed a highly polarized visual scene tilted ±112° while lying supine on the European Space Agency's short-arm human centrifuge. The centrifuge was rotated to simulate 24 logarithmically spaced g-levels along the long axis of the body (0.04-0.5g at ear-level). The perception of upright was measured using the Oriented Character Recognition Test (OCHART). OCHART uses the ambiguous symbol "p" shown in different orientations. Participants decided whether it was a "p" or a "d" from which the perceptual upright (PU) can be calculated for each visual/gravity combination. The relative contribution of vision, gravity and the internal representation of the body were then calculated. Experiments were repeated while upright. The relative contribution of vision on the PU was less in females compared to males (t=-18.48, p≤0.01). Females placed more emphasis on the gravity cue instead (f:28.4%, m:24.9%) while body weightings were constant (f:63.0%, m:63.2%). When upright (1g) in this and other studies (e.g., Barnett-Cowan et al. 2010, EJN, 31,1899) females placed more emphasis on vision in this task than males. The reduction in weight allocated by females to vision when in simulated low-gravity conditions compared to when upright under normal gravity may be related to similar female behaviour in response to other instances of visual-vestibular conflict. Why this is the case and at which point the perceptual change happens requires further research.
Design and Analysis of an OFDM-Based Orthogonal Chaotic Vector Shift Keying Communication System
(2018)
We propose a new non-coherent multicarrier spread-spectrum system that combines orthogonal chaotic vector shift keying (OCVSK) and orthogonal frequency-division multiplexing (OFDM). The system enhances OCVSK by sending multiple groups of information sequences with the same orthogonal chaotic vector reference sequences over the selected subcarriers. Each group carries M information bits and is separated from other groups by orthogonal chaotic reference signals. We derive the information rate enhancement (IRE) and the energy saving enhancement (ESE) factors as well as the bit error rate theory of OFDM-OCVSK under additive white Gaussian noise and multipath Rayleigh fading channels and compare the results with conventional OCVSK systems. For large group numbers, the results show that the IRE and ESE factors approachM×100% andM/(M+1)×100%, respectively, and thus outperform OCVSK systems. The complexity analysis of the proposed scheme as compared with OFDM-DCSK shows a significant reduction in the number of complex multiplications required.
In 2018, in the US alone, it is estimated that 268,670 people will be diagnosed with breast cancer, and that 41,400 will die from it. Since breast cancers often become resistant to therapies, and certain breast cancers lack therapeutic targets, new approaches are urgently required. A cell-stress response pathway, the unfolded protein response (UPR), has emerged as a promising target for the development of novel breast cancer treatments. This pathway is activated in response to a disturbance in endoplasmic reticulum (ER) homeostasis but has diverse physiological and disease-specific functions. In breast cancer, UPR signalling promotes a malignant phenotype and can confer tumours with resistance to widely used therapies. Here, we review several roles for UPR signalling in breast cancer, highlighting UPR-mediated therapy resistance and the potential for targeting the UPR alone or in combination with existing therapies.
Once aberrantly activated, the Wnt/βcatenin pathway may result in uncontrolled proliferation and eventually cancer. Efforts to counter and inhibit this pathway are mainly directed against βcatenin, as it serves a role on the cytoplasm and the nucleus. In addition, speciallygenerated lymphocytes are recruited for the purpose of treating liver cancer. Peripheral blood mononuclear lymphocytes are expanded by the timely addition of interferon γ, interleukin (IL)1β, IL2 and anticluster of differentiation 3 antibody. The resulting cells are called cytokineinduced killer (CIK) cells. The present study utilised these cells and combine them with drugs inhibiting the Wnt pathway in order to examine whether this resulted in an improvement in the killing ability of CIK cells against liver cancer cells. Drugs including ethacrynic acid (EA) and ciclopirox olamine (CPX) were determined to be suitable candidates, as determined by previous studies. Drugs were administered on their own and combined with CIK cells and then a cell viability assay was performed. These results suggest that EAtreated cells demonstrated apoptosis and were significantly affected compared with untreated cells. Unlike EA, CPX killed normal and cancerous cells even at low concentrations. Subsequent to combining EA with CIK cells, the potency of killing was increased and a greater number of cells died, which proves a synergistic action. In summary, EA may be used as an antihepatocellular carcinoma drug, while CPX possesses a high toxicity to cancerous as well as to normal cells. It was proposed that EA should be integrated into present therapeutic methods for cancer.