Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans

A growing body of evidence indicates that P2X receptors (P2XRs), a family of ligand-gated cation channels activated by extracellular ATP, play an important role in pain signaling. In contrast to the role of the P2X₃R subtype that has been extensively studied, the precise roles of others among the seven P2XR subtypes (P2X₁R-P2X₇R) remain to be determined because of a lack of sufficiently powerful tools to specifically block P2XR signaling in vivo. In the present study, we investigated the behavioral phenotypes of a line of mice in which the p2rx4 gene was disrupted in a series of acute and chronic pain assays. While p2rx4 ^-/- mice showed no major defects in pain responses evoked by acute noxious stimuli and local tissue damage or in motor function as compared with wild-type mice, these mice displayed reduced pain responses in two models of chronic pain (inflammatory and neuropathic pain). In a model of chronic inflammatory pain developed by intraplantar injection of complete Freund's adjuvant (CFA), p2rx4 ^-/- mice exhibited attenuations of pain hypersensitivity to innocuous mechanical stimuli (tactile allodynia) and also of the CFA-induced swelling of the hindpaw. A most striking phenotype was observed in a test of neuropathic pain: tactile allodynia caused by an injury to spinal nerve was markedly blunted in p2rx4 ^-/- mice. By contrast, pain hypersensitivity to a cold stimulus (cold allodynia) after the injury was comparable in wild-type and p2rx4 ^-/- mice. Together, these findings reveal a predominant contribution of P2X₄R to nerve injury-induced tactile allodynia and, to the lesser extent, peripheral inflammation. Loss of P2X₄R produced no defects in acute physiological pain or tissue damaged-induced pain, highlighting the possibility of a therapeutic benefit of blocking P2X₄R in the treatment of chronic pain, especially tactile allodynia after nerve injury.     

Effect of temperature difference between manikin and wet fabric skin surfaces on clothing evaporative resistance: how much error is there?

Clothing evaporative resistance is one of the inherent factors that impede heat exchange by sweating evaporation. It is widely used as a basic input in physiological heat strain models. Previous studies showed a large variability in clothing evaporative resistance both at intra-laboratory and inter-laboratory testing. The errors in evaporative resistance may cause severe problems in the determination of heat stress level of the wearers. In this paper, the effect of temperature difference between the manikin nude surface and wet textile skin surface on clothing evaporative resistance was investigated by both theoretical analysis and thermal manikin measurements. It was found that the temperature difference between the skin surface and the manikin nude surface could lead to an error of up to 35.9% in evaporative resistance of the boundary air layer. Similarly, this temperature difference could also introduce an error of up to 23.7% in the real clothing total evaporative resistance (R _{et_real}  < 0.1287 kPa m²/W). Finally, it is evident that one major error in the calculation of evaporative resistance comes from the use of the manikin surface temperature instead of the wet textile fabric skin temperature.     

A review of the lichen family Parmeliaceae – history,phylogeny and current taxonomy

The largest family of lichen‐forming fungi, the Parmeliaceae, is reviewed. It includes 79 genera in current use and ca 2726 species, a large majority of which belong to one of five main clades: the parmelioid, cetrarioid, usneoid, alectorioid and hypogymnioid. However, 21 genera are positioned outside these clades, and four genera in current use still lack DNA‐ data. The family has been shown to be monophyletic and the generic classification is relatively well‐settled compared with other lecanoralean families. Each clade and its genera are presented here with the latest results from phylogenetic analyses and current taxonomy. In addition, a historical outline of the family and its most prominent researchers is provided.     

Silk—A new substrate for UDP-d-xylose: Proteoglycan core protein β-d-xylosyltransferase

The formation of most connective tissue polysaccharides is initiated by transfer of d-xylose from UDP-d-xylose to specific serine residues in the core proteins of the putative proteoglycans. The substrate specificity of the xylosyltransferase catalyzing this reaction has not yet been examined in detail, but it appears that a -Ser-Gly- pair is an essential part of the substrate structure. Since the preparation of the known acceptors (e.g., Smith-degraded or HF-treated cartilage proteoglycan) involves a substantial effort, we have searched for readily available proteins with the -Ser-Gly-sequence, which might serve as alternative substrates. In the present work, it was found that silk fibroin from Bombyx mori, which consists, in large part, of the repeating hexapeptide, Ser-Gly-Ala-Gly-Ala-Gly, is an excellent substrate for the xylosyltransferase from embryonic chick cartilage. Pieces of silk were used directly in the reaction mixtures, and [¹⁴C]xylose transferred from UDP-d-[¹⁴C]xylose was measured by liquid scintillation spectrometry after rinsing the silk in 1 m NaCl and water. Substantially greater incorporation was observed with preparations of silk or fibroin which had been dissolved in 60% LiSCN and subsequently dialyzed exhaustively or diluted appropriately. Under standard reaction conditions, the V_max for fibroin was 531 pmol/h/mg enzyme protein, as compared to 223 pmol/h/mg for Smith-degraded proteoglycan. K_m values were 182 mg/liter (fibroin) and 143 mg/liter (Smith-degraded proteoglycan). The product of [¹⁴C]xylose transfer to silk was alkali labile, and [¹⁴C]xylitol was formed when [¹⁴C]xylosylsilk was treated with borohydride in alkali. Proteolytic digestion with papain, Pronase, leucine aminopeptidase, and carboxypeptidase A yielded a radioactive product which was identified as [¹⁴C]xylosylserine by electrophoresis and chromatography. The identity of the isolated [¹⁴C]xylosylserine was further supported by its resistance to treatment with alkali (0.5 m KOH: 100°C; 8h) and by acid hydrolysis which yielded [¹⁴C]xylose. Tryptic and chymotryptic fragments from fibroin were also good xylose acceptors and had V_max values 60–70% of that observed for the intact protein. Substantial acceptor activity was displayed also by the sericin fraction of silk and by the silk sequence hexapeptide, Ser-Gly-Ala-Gly-Ala-Gly; the latter had a V_max value close to 20% of that of intact fibroin.     

Inhibition of polyamine synthesis reduces the growth rate and delays the expression of differentiated phenotypes in primary cultures of embryonic mesoderm from chick

Summary Inhibition of polyamine synthesis in early chick embryos blocks their development at gastrulation. Analyses of arrested embryos show that mesodermal outgrowth and differentiation are drastically impaired. To study these effects in greater detail, we have used primary cultures of embryonic mesoderm from chick. The cultures were treated with -difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, the first and rate-limiting enzyme in polyamine synthesis. In control culture medium, mesodermal cells retained their in ovo outgrowth behavior and differentiation pattern. Addition of 10 mM DFMO to the culture medium, however, retarded attachment and outgrowth, and reduced the rate of proliferation of the mesodermal cells. Furthermore, the expression of differentiated phenotypes, such as beating heart tissue, erythroid cells, and adipocyte-like cells, was delayed. Simultaneous addition of 100 M putrescine prevented or reduced the effects of DFMO, showing that these were indeed caused by polyamine deficiency. In the DFMO-treated mesoderm, DNA synthesis was markedly suppressed by the first day. Similar effects on RNA and protein synthesis developed at a later time. Our data suggest that a reduction in the concentrations of the polyamines decreases the rate of mesodermal cell proliferation, and as a conseqence delays the expression of differentiated phenotypes.     

Treatment of artificially induced storage disease with lysosomotropic microparticles

An artificial storage disease has been induced in mice by intravenously injecting 14C-labelled crosslinked dextran. The dextran was essentially taken up in the spleen and liver by cells belonging to the reticuloendothelial system and stored there in the lysosomes. Soluble dextranase, when given intravenously, had no effect on the stored dextran as judged by the radioactivity content of the tissues. However, when the dextranase was immobilized in microparticles of polyacryldextran and injected intravenously, the clearance of the radiolabelled dextran was significantly catalyzed. The lysosomotropic microparticles carried the enzyme to the lysosomes, where the microparticles were destroyed by the dextranase, which thereafter digested the stored 14C-dextran. The results illustrate the use of "self-destroying" microparticles as a lysosome-directed carrier of enzymes.     

Solar heat load on man

Different methods have been compared for the estimation of solar heat load on man. The comparison comprised several methods based on the calculation of absorbed solar radiation and one method for calculation of mean radiant temperature (Mrt). Regression analysis was carried out for predicted values and values calculated for a vertical cylinder, assumed as an analog model of a standing man. Regression of mean skin temperature, measured in 10 subjects exposed to solar radiation under a variety of climatic conditions, on predicted radiant heat load was also analysed. Mean skin temperature correlated best withMrt, accounting for more than 50% of the variance. The results indicated that three methods provide a realistic estimation of the radiation heat load, whereas some methods show deviations of several hundred per cent.