Binding affinities and activation of Asp712Ala and Cys100Ser mutated kinin B1 receptor forms suggest a bimodal scheme for the molecule of bound-DABK

AbstractMutant forms of kinin B1 receptor (B1R) and analogs of the full agonist des-Arg9-bradykinin (DABK) were investigated aiming to verify the importance of selected receptor residues and of each agonist-peptide residue in the specific binding and activation. Linked by a specific disulfide bond (Cys100–Cys650), the N-terminal (Nt) and the EC3 loop C-terminal (Ct) segments of angiotensin II (AngII) receptor 1 (AT1R) have been identified to form an extracellular site for binding the agonist Nt segment (Asp1 and Arg2 residues). Asp712 residue at the receptor EC3 loop binds the peptide Arg2 residue. By homology, a similar site might be considered for DABK binding to B1R since this receptor contains the same structural elements for composing the site in AT1R, namely the disulfide bond and the EC3 loop Asp712 residue. DABK, Alan-DABK analogs (n=Ala1-, Ala2-, Ala3-, Ala4-, Ala5-, Ala6-, Ala7-, Ala8-DABK), and other analogs were selected to binding wild-type, Asp712Ala and Cys100Ser mutated B1R receptors. The results obtained suggested that the same bimodal scheme adopted for AngII-AT1R system may be applied to DABK binding to B1R. The most crucial similarity in the two cases is that the Nt segments of peptides equally bind to the homologous Asp712 residue of both AT1R and B1R extracellular sites. Confirming this preliminary supposition, mutation of residues located at the B1R extracellular site as EC3 loop Asp712 and Cys100 caused the same modifications in biological assays observed in AT1R submitted to homologous mutations, such as significant weakening of agonist binding and reduction of post-receptor-activation processes. These findings provided enough support for defining a site that determines the specific binding of DABK to B1R receptors

Use Of Different Electrical Stimulations For Treating Pain In Women With Temporomandibular Disorders [utilização De Diferentes Estimulações Elétricas Para O Tratamento Da Dor Em Mulheres Com Disfunção Temporomandibular]

Objective: To analyze pain intensity in individuals with temporomandibular disorder (TMD) who were treated with ten sessions of transcutaneous electrical nerve stimulation (TENS) or high voltage electrical stimulation (HVES). Methods: Twenty-four women (22.98±1.86 years old) with a diagnosis of TMD in accordance with the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were selected. Sixty percent of the participants had a diagnosis of TMD classified as group Ia and 40% as Ia and IIa. They were divided into two groups named TENS group (TG) and high-voltage group (HVG). Each participant received ten applications of either TENS (10Hz, modulated at 50%, 200μs and motor threshold intensity) or HVES (10Hz, twin pulses of 20μs each at intervals of 100μs between the twin pulses, 100volts and positive pole) twice a week for 30 minutes. To measure the pain intensity, a visual analog scale (VAS) was used. Statistical analyses were performed using t test and simple linear regression. Results: Comparison of the pre- and post-TENS conditions showed diminished pain intensity (p<0.05) in most sessions except for sessions 6, 7 and 8. In contrast, HVES reduced the pain intensity in all sessions (p<0.05). Evaluation of the pre-application values showed that both treatments decreased the pain intensity uniformly over the ten sessions (p<0.05). Conclusions: TENS and HVES both promoted reductions in pain intensity in women with TMD. HVES is a therapeutic resource recommended for such patients. © 2009 Revista Brasileira de Fisioterapia.126476481Tvrdy, P., Methods of imaging in the diagnosis of temporomandibular joint disorders (2007) Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 151 (1), pp. 133-6Magnusson, T., Egermark, I., Carlsson, G.E., A longitudinal epidemiologic study of signs and symptoms of temporomandibular disorders from 15 to 35 years of age (2000) J Orofac Pain, 14 (4), pp. 310-9Oliveira, A.S., Bermudez, C.C., Souza, R.A., Souza, C.M.F., Dias, E.M., Castro, C.E.S., Impacto da dor na vida de portadores de disfunção temporomandibular (2003) J Appl Oral Sci, 11 (2), pp. 138-43Furto, E.S., Cleland, J.A., Whitman, J.M., Olson, K.A., Manual physical therapy interventions and exercise for patients with temporomandibular disorders (2006) Cranio, 24 (4), pp. 283-91Cappelini, V.K., Souza, G.S., Faria, C.R.S., Massage therapy in the management of myogenic TMD: a pilot study (2006) J Apllied Oral Sci, 14 (1), pp. 21-6Kato, M.T., Kogawa, E.M., Santos, C.N., Conti, P.C.R., Tens and low-level laser therapy in the Management of temporomandibular Disorders (2006) J Appl Oral Sci, 14 (2), pp. 130-5Alvarez-Arenal, A., Junquera, L.M., Fernandez, J.P., Gonzalez, I., Olay, S., Effect of occlusal splint and transcutaneous electric nerve stimulation on the signs and symptoms of temporomandibular disorders in patients with bruxism (2002) J Oral Rehabil, 29 (9), pp. 858-63Rodrigues, D., Siriani, A.O., Bérzin, F., Effect of conventional TENS on pain and eletromyographic activity of masticatory muscles in TMD patients (2004) Braz Oral Res, 18 (4), pp. 290-5Windt, D.A., Heijden, G.J., Berg, S.G., Riet, G., Winter, A.F., Bouter, L.M., Ultrasound therapy for musculoskeletal disorders: a systematic review (1999) Pain, 81 (3), pp. 257-71Gonçalves, R.N., Ordenes, I.E.U., Rodrigues-Bigaton, D., Efeito indireto da TENS sobre os músculos cervicais em portadores de DTM (2007) Fisioter Mov, 20 (2), pp. 83-90Linde, C., Isacsson, G., Jonsson, B.G., Outcome of 6-week treatment with transcutaneous electric nerve stimulation compared with splint on symptomatic temporomandibular joint disk displacement without reduction (1995) Acta Odontol Scand, 53 (2), pp. 92-8Stralka, S.W., Jackson, J.A., Lewis, A.R., Treatment of hand and wrist pain: A randomized clinical trial of high voltage pulsed, direct current built into a wrist splint (1998) AAOHN Journal, 46 (5), pp. 233-6Holcomb, W.R., A practical Guide to Electrical Therapy (1997) J Sport Rehabil, 6, pp. 272-82Nelson, R.M., Hayes, K.W., Currier, D.P., (2003) Eletroterapia Clínica, , 3a ed. Barueri: ManoleAlon, G., Os princípios da estimulação elétrica (2003) Eletroterapia Clínica, pp. 55-139. , In. Nelson RM, Hayes KW, Currier DP. 3a ed. Barueri: ManoleIdo, C., Rothenbuhler, R., Janz, L., Eletroestimulação nervosa trancutânea de baixa freqüência nos "tender points" dos pacientes fibromioálgicos juvenis (2003) Rev Fisioter Univ São Paulo, 10 (1), pp. 1-6Larsson, S.E., Bodegard, L., Henriksson, K.G., Oberg, P.A., Chronic trapezius myalgia. Morphology and blood flow studied in 17 patients (1990) Acta Orthop Scand, 61 (5), pp. 394-8Tullberg, M., Alstergren, P.J., Ernberg, M.M., Effects of low-power laser exposure on masseter muscle pain and microcirculation (2003) Pain, 105 (1-2), pp. 89-96Okada, K., Yamaguchi, T., Minowa, K., Inoue, N., The influence of hot pack therapy on the blood flow in masseter muscles (2005) J Oral Rehabil, 32 (7), pp. 480-6Wieselmann-Penkner, K., Janda, M., Lorenzoni, M., Polansky, R., A comparison of the muscular relaxation effects of TENS and EMG-biofeedback in patients with bruxism (2001) J Oral Rehabil, 28 (9), pp. 849-53Cramp, A.F.L., Gilsenan, C., Lowe, A.S., Walsh, D.M., The effect of high- and low-frequency transcutaneous electrical nerve stimulation upon cutaneous blood flow and skin temperature in healthy subjects (2000) Clin Physiol, 20 (2), pp. 150-7Goldman, R., Brewley, B., Zhou, L., Golden, M., Electrotherapy reverses inframalleolar ischemia: A retrospective, observational study (2003) Advances in Skin & Wound care, 16 (2), pp. 79-89Goldman, R., Rosen, M., Brewley, B., Golden, M., Electrotherapy promotes healing and microcirculation of infrapopliteal ischemic wounds: a prospective pilot study (2004) Adv Skin Wound Care, 17 (6), pp. 284-94Robinson, A.J., Snyder, M.L., (2001) Eletrofisiologia Clínica: eletroterapia e teste eletrofisiológico, , 2a ed. Porto Alegre: Artme

Technical and economic pre-feasibility study for the construction of septic tank-filter-sinkhole with alternative material

Received: February 2nd, 2021 ; Accepted: August 3rd, 2021 ; Published: August 24th, 2021 ; Correspondence: [email protected] study of the different materials used in the construction of septic tanks aims to facilitate and spread the use of this sewage treatment system in places that are not assisted by municipal sewage systems and in the rural area, which despite having a smaller number of inhabitants compared to the urban area This study aims to carry out a technical and economic evaluation of the concrete and tires using in the construction of septic tanks-filter-sinkhole. The wastewater treatment systems were built according to the recommendations in NBR 7229/93 and 13969/97. To evaluate the efficiency of each system built, the following parameters were analyzed: chemical oxygen demand (COD), the potential of hydrogen (pH), alkalinity, acidity, and temperature. In the economic evaluation, the materials and labor required to install the systems were considered using the Brazilian cost database (SINAPI), and an economic and financial feasibility study was carried out. According to the technical and economic analysis of construction, both systems showed the same technical performance, however, the concrete design proved to be more advantageous than the tire design, considering the difficulty in acquiring the tires and the high cost if it is necessary to buy them, in addition to the greater difficulty in handling and installing the tire system compared to the concrete one

Valorization of lignin side-streams into polyols and rigid polyurethane foams—a contribution to the pulp and paper industry biorefinery

Valorization of industrial low-value side-streams are of great interest, contributing to boosts in the circular economy. In this context, lignin side-streams of the pulp and paper industry were oxypropylated to produce biobased polyols and tested in the synthesis of rigid polyurethane (RPU) foams. E. globulus lignins, namely a lignin isolated from an industrial Kraft black liquor and depolymerized lignins obtained as by-products of an oxidation process, were used. RPU foams, synthesized with 100% lignin-based polyols and using a 1.1 NCO/OH ratio, were characterized concerning apparent density, morphology, thermal conductivity, thermal stability, and heat release rate (HRR). Foams containing the lignin-based polyols presented densities varying from 44.7 to 112.2 kg/m3 and thermal conductivity in the range of 37.2–49.0 mW/mK. For the reference foam (sample produced with 100% wt. Daltofoam TP 32015 polyol), values of 70.9 kg/m3 and 41.1 mW/mK were obtained, respectively. The achieved results point out the viability of using the generated lignin-based polyols at 100% content in RPU foams, mainly when depolymerized lignins are used. Moreover, fire retardancy was favored when the lignin-based polyols were introduced. The proposed strategies can contribute to establishing the integrated pulp and paper biorefinery concept where material synthesis (polyols and RPU foams) can be combined with chemical production (vanillin and syringaldehyde).Foundation for Science and Technology (FCT, Portugal) and FEDER under Program PT2020 for financial support to CIMO (UIDB/00690/2020), and to UIDB/50020/2020 of the Associate Laboratory LSRE-LCM—funded by national funds through FCT/MCTES (PIDDAC); national funding by FCT, PI, through the institutional scientific employment program contract for Isabel P. Fernandes. This work was carried out under the Project No. 33969 Bioblocks—Design of biobased products from renewable lignocellulosic sources as precursors for the bioindustry of chemical synthesis and biomaterials—financed by FEDER through the Operational Program for Competitiveness Factors (POFC) and QREN. To COST Action LignoCOST (CA17128) supported by COST (European Cooperation in Science and Technology).info:eu-repo/semantics/publishedVersio

Managing groundwater supplies subject to drought: perspectives on current status and future priorities from England (UK)

Effective management of groundwater resources during drought is essential. How is groundwater currently managed during droughts, and in the face of environmental change, what should be the future priorities? Four themes are explored, from the perspective of groundwater management in England (UK): (1) integration of drought definitions; (2) enhanced fundamental monitoring; (3) integrated modelling of groundwater in the water cycle; and (4) better information sharing. Whilst these themes are considered in the context of England, globally, they are relevant wherever groundwater is affected by drought

IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages.

CD4+ T cells are crucial to the development of CD8+ T cell responses against hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+ T cells initiate a seemingly normal differentiation and proliferation during the first few days after immunization. However, this response fails to develop further and is reduced by more than 90%, compared to that observed in the presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by CD4+ T cells is essential to the full development of this CD8+ T cell response. This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk leading to the development of immunity against an infectious pathogen

Purification And N-terminal Sequencing Of Two Presynaptic Neurotoxic Pla2, Neuwieditoxin-i And Neuwieditoxin-ii, From Bothrops Neuwiedi Pauloensis (jararaca Pintada) Venom

Two presynaptic phospholipases A2 (PLA2), neuwieditoxin-I (NeuTX-I) and neuwieditoxin-II (NeuTX-II), were isolated from the venom of Bothrops neuwiedi pauloensis (BNP). The venom was fractionated using molecular exclusion HPLC (Protein-Pak 300SW column), followed by reverse phase HPLC (μBondapak C18 column). Tricine-SDS-PAGE in the presence or absence of dithiothreitol showed that NeuTX-I and NeuTX-II had a molecular mass of approximately 14 kDa and 28kDa, respectively. At 10μg/ml, both toxins produced complete neuromuscular blockade in indirectly stimulated chick biventer cervicis isolated preparation without inhibiting the response to acetylcholine, but NeuTX-II reduced the response to KCl by 67.0±8.0% (n=3; p&lt;0.05). NeuTX-I and NeuTX-II are probably responsible for the presynaptic neurotoxicity of BNP venom in vitro. In fact, using loose patch clamp technique for mouse phrenic nerve-diaphragm preparation, NeuTX-I produced a calcium-dependent blockade of acetylcholine release and caused appearance of giant miniature end-plate potentials (mepps), indicating a pure presynaptic action. The N-terminal sequence of NeuTX-I was DLVQFGQMILKVAGRSLPKSYGAYGCYCGWGGRGK (71% homology with bothropstoxin-II and 54% homology with caudoxin) and that of NeuTX-II was SLFEFAKMILEETKRLPFPYYGAYGCYCGWGGQGQPKDAT (92% homology with Basp-III and 62% homology with crotoxin PLA2). The fact that NeuTX-I has Q-4 (Gln-4) and both toxins have F-5 (Phe-5) and Y-28 (Tyr-28) strongly suggests that NeuTX-I and NeuTX-II are Asp49 PLA2.131103121AIRD, S.D., KAISER II, LEWIS RV., KRUGGEL WG. A complete amino acid sequence for the basic subunit of crotoxin (1986) Arch. Biochem. Biophys, 249, pp. 296-300AIRD, S.D., KRUGGEL, W.G., KAISER II, Amino acid sequence of the basic subunit of Mojave toxin from the venom of the Mojave rattlesnake (Crotalus s. scutulatus) (1990) Toxicon, 28, pp. 669-673BEGHINI, D.G., TOYAMA, M.H., HYSLOP, S., SODEK, L., NOVELLO, J.C., MARANGONI, S., Enzymatic characterization of a novel phospholipase A2 from Crotalus durissus cascavella rattlesnake (maracambóia) venom (2000) J. Protein Chem, 19, pp. 603-607BORJA-OLIVEIRA, C.R., DURIGON, A.M., VALLIN, A.C.C., TOYAMA, M.H., SOUCCAR, C., MARANGONI, S., RODRIGUES-SIMIONI, L., The pharmacological effects of Bothrops neuwiedi pauloensis (jararaca-pintada) snake venom on avian neuromuscular transmission (2003) Braz. J. Med. Biol. Res, 36, pp. 617-624BORJA-OLIVEIRA, C.R., SOARES, A.M., ZAMUNER, S.R., HYSLOP, S., GIGLIO, J.R., PRADO-FRANCESCHI, J., RODRIGUES-SIMIONI, L., Intraspecific variation in the neurotoxic and myotoxic activities of Bothrops neuwiedi snake venoms (2002) J. Venom. Anim. Toxins, 8, pp. 88-101BUCARETCHI, F., HERRERA, S.R.F., HYSLOP, S., BARACAT, E.C.E., VIEIRA, R.J., Snakebites by Bothrops spp in children in Campinas, São Paulo, Brazil (2001) Rev. Inst. Med. Trop. São Paulo, 43, pp. 329-333CHO, W., KEZDY, F.J., Chromogenic substrate and assay of phospholipase A 2 (1991) Meth. Enzymol, 197, pp. 75-79CINTRA, A.C., MARANGONI, S., OLIVEIRA, B., GIGLIO, J.R., Bothropstoxin-I: Amino acid sequence and function (1993) J. Protein Chem, 12, pp. 57-64COGO, J.C., PRADO-FRANCESCHI, J., CRUZ-HÖFLING, M.A., CORRADO, A.P., RODRIGUES-SIMIONI, L., Effects of Bothrops insularis on the mouse and chick nerve-muscle preparation (1993) Toxicon, 31, pp. 1237-1247COGO, J.C., PRADO-FRANCESCHI, J., GIGLIO, J.R., CORRADO, A.P., CRUZ-HÖFLING, M.A., DONATO, J.L., LEITE, G.B., RODRIGUES-SIMIONI, L., An unusual presynaptic action of Bothrops insularis snake venom mediated by phospholipase A2 fraction (1998) Toxicon, 36, pp. 1323-1332DE SOUSA, M.V., MORHY, L., ARNI, R.K., WARD, R.J., GUTIÉRREZ, J.M., Amino acid sequence of a myotoxic Lys-49-phospholipase A2 homologue from the venom of Cerrophidion (Bothrops) godmani (1998) Biochim. Biophys. Acta, 1384, pp. 204-208DURIGON, A.M., BORJA-OLIVEIRA, C.R., DAL, B.C., OSHIMA-FRANCO, Y., COGO, J.C., LAPA, A.J., SOUCCAR, C., RODRIGUES-SIMIONI, L., Neuromuscular activity of Bothrops neuwiedi pauloensis snake venom in mouse nerve-muscle preparations (2005) J. Venom. Anim. Toxins incl. 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