Genetic properties of transposons Tn6-1, Tn6-2 and Tn19-1

The level and range transposition of the transposons Tn6-1, Tn6-2, Tn19-1, and their ability to influence plasmid transfer has been studied. The widest range of transposition was shown for transposon Tn6-2. Insertions of each of the studied transposons into different conjugative plasmids genomes resulted in change of frequencies of plasmids transfer and change of plasmids mobilization activity.     

Conformational and biological characterization of human parathyroid hormone hPTH(1-34) analogues containing beta-amino acid residues in positions 17-19

The N-terminal 1-34 fragment of parathyroid hormone (PTH) elicits the full spectrum of bone-related biological activities of the intact native sequences. It has been suggested that the structural elements essential for bioactivity are two helical segments located at the N-terminal and C-terminal sequences, connected by hinges or flexible points around positions 12 and 19. In order to assess the relevance of the local conformation around Gly(18) upon biological function, we synthesized and characterized the following human (h) PTH(1-34) analogues containing beta-amino acid residues: [analogues: see text]. Biological activity and binding affinity of analogue I are one order of magnitude lower than those of the parent compound. In analogue II, both binding affinity and biological activity are partially recovered. Analogues III and V have no binding affinity and very low biological activity. Both bioactivity and binding affinity are partially recovered in analogue IV. The conformational properties of the analogues in aqueous solution containing dodecylphosphocholine micelles were studied by CD, 2D-nuclear magnetic resonance and molecular dynamics calculations. The results confirmed the presence in all analogues of two helical segments located at the N-terminal and C-terminal sequences. The insertion of beta-amino acid residues around position 18 does not cause appreciable conformational differences in the five analogues. The differences in biological activity and binding affinity among the five analogues cannot be related to structural differences in the membrane mimetic environment reported in this study. Our results stress the importance of the side-chain functionalities in the sequence 17-19 for biological function.     

Growth hormone response to growth hormone releasing hormone 1-40 in Turner's syndrome

The response of growth hormone (GH) to acute administration of GH-releasing hormone 1-40 (GHRH) was evaluated in 12 patients with Turner's syndrome and in 12 prepubertal or early pubertal girls. In 7 of 12 patients GHRH induced a definite increase (greater than 10 ng/ml) of plasma GH levels. In 5 patients there was a poor GH rise after GHRH administration (less than 10 ng/ml). Overall, the mean GH response of patients was significantly lower than that of normal girls. Five out of 7 patients with a 45 X,O karyotype had a reduced GH rise after GHRH, while all patients with non X,O karyotype (mosaicism and/or 46 X,iX) had a normal GH response to GHRH. Although the cause of short stature in patients with Turner's syndrome is most likely multifactorial, a reduced pituitary GH reserve, as documented by the reduced GH response to GHRH in some of our patients, may contribute to the growth impairment in this disorder.     

血清CEA、CA19-9、CYFRA21-1与结直肠腺癌的相关性分析

目的:探究血清癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原19-9、细胞角蛋白19片段(cytokeratin19 fragements,CYFRA21-1)与结直肠腺癌的病理相关性。方法:选择于我院接受治疗的80例结直肠腺癌患者为病例组,选择同期于我院接受治疗的50例良性结直肠病变患者为良性对照组,选择我院体格检查的50例健康个体为对照组,分别采集三组个体的血样并进行CEA、CA19-9以及CYFRA21-1水平的检测,并比对三组个体上述因子阳性表达率、因子水平,同时分析三种因子同结直肠腺癌患者TNM分期相关性,最后探究三种因子对结直肠腺癌的诊断价值。结果:(1)以CEA≥2.805μg/L、CA19-9≥39 U/m L、CYFR21-1≥3.3 ng/mL为临界值,结果显示病例组CEA阳性率51.25%,CA19-9阳性率31.25%,CYFR21-1阳性率40.00%,明显高于良性组的10.00%、20.00%和10.00%,高于对照组的8.00%、12.00%和2.00%(P<0.05);(2)比较显示病例组患者的CEA、CA19-9以及CYFR21-1水平明显高于良性对照组以及对照组(P<0.05),良性对照组CEA、CA19-9以及CYFR21-1水平明显高于对照组(P<0.05);(3)比较显示IV期结直肠腺癌患者CEA、CA19-9以及CYFRA21-1水平明显高于III期以及I+II期(P<0.05),III期三种因子水平明显高于I+II期(P<0.05);(4)CEA对结直肠腺癌诊断一致性71.25%,灵敏度65.00%,特异度90.00%;CA19-9诊断一致性46.25%,灵敏度35.00%,特异度80.00%;CYFRA21-1诊断一致性55.00%,灵敏度46.67%,特异度80.00%;联合诊断一致性95.00%,灵敏度95.00%,特异度95.00%。结论:血清CEA、CA19-9以及CYFRA21-1对结直肠腺癌具有较明确的诊断价值,不同病理分期患者中表达差异明显,可以考虑将联合诊断作为结直肠腺癌鉴别方式之一,推广于临床中。     

Solution structures of human parathyroid hormone fragments hPTH(1-34) and hPTH(1-39) and bovine parathyroid hormone fragment bPTH(1-37)

Parathyroid hormone (PTH) is involved in regulation of the calcium level in blood and has an influence on bone metabolism, thus playing a role in osteoporosis therapy. In this study, the structures of the human PTH fragments (1-34) and (1-39) as well as bovine PTH(1-37) in aqueous buffer solution under near physiological conditions were determined using two-dimensional nuclear magnetic resonance spectroscopy. The overall structure of the first 34 amino acids of these three peptides is virtually identical, exhibiting a short NH(2)-terminal and a longer COOH-terminal helix as well as a defined loop region from His14 to Ser17, stabilized by hydrophobic interactions. bPTH(1-37), which has a higher biological activity, shows a better-defined NH(2)-terminal part. In contrast to NH(2)-terminal truncations, which cause destabilization of helical structure, neither COOH-terminal truncation nor elongation significantly influences the secondary structure. Furthermore, we investigated the structure of hPTH(1-34) in 20% trifluoroethanol solution. In addition to its helix-stabilizing effect, trifluorethanol causes the loss of tertiary hydrophobic interactions.     

Conformational and biological properties of glucagon fragments containing residues 1-17 and 19-29

The 29 amino acid polypeptide hormone glucagon was cleaved into two large fragments by the enzyme clostripain. The conformational properties of these two fragments were monitored by circular dichroism at pH 2 and 12 in both the presence and absence of sodium dodecyl sulfate. Both glucagon (1-17) and glucagon (19-29) have reduced abilities to fold in aqueous solution. However, both fragments can take on structure of higher apparent helical content in acidic solution in the presence of sodium dodecyl sulfate but only the glucagon (19-29) retains this conformation at high pH. Neither of the two fragments react with dimyristoylphosphatidylcholine as the intact peptide does. Only the carboxyl terminal fragment was capable of reacting with an antibody specific for glucagon. The glucagon (1-17) has markedly reduced affinity for binding to the glucagon receptor as well as markedly reduced ability to stimulate adenylate cyclase activity which is not affected by the presence of glucagon (19-29). It is proposed that the intact sequence provides specific groups required for activity as well as the potential for forming a stable amphipathic helix, both of which are necessary for full biological activity at low peptide concentrations.     

Expression and regulation of miR-1, -133a, -206a, and MRFs by thyroid hormone during larval development in Paralichthys olivaceus

MiR-1, miR-133a, and miR-206a have been identified as muscle-specific miRNAs. They play multiple crucial roles in the regulation of muscle development. Here, we show that these miRNAs were differentially expressed during the larval development of flounder, and specifically expressed in skeletal muscle and heart in adult tissues/organs. The expression levels of these miRNAs were significantly changed by thyroid hormone (TH) or thiourea (TU) treatment during metamorphosis from 17 dph (days post hatching) to 42 dph. In addition, the expression levels of MyoD and Myf5 mRNAs markedly increased at 14 dph (pre-metamorphosis) compared to metamorphic stages, and their expression levels are far above the myogenin during larval development. Moreover, these MRFs (myogenic regulatory factors) expression were directly or indirectly regulated by thyroid hormone or thiourea during metamorphosis. All the results suggest that miRNAs and MRFs might be involved in signaling pathway of TH or TU-mediated flounder metamorphosis.     

Parathyroid hormone (1-34) and Nleu8,18Tyr34-parathyroid hormone, (3-34) amide increase diacylglycerol in neonatal mouse calvaria.

Previously, we and others have presented evidence that a calcium second messenger system is involved in the action of parathyroid hormone (PTH) on bone. In the present report, the effects of PTH(1-34) and PTH(3-34)amide treatment on diacylglycerol (DG) in neonatal mouse calvaria are described. PTH(1-34) produced a rapid (within 5 minutes) increase in calvarial incorporation of 3H-arachidonic acid into DG. The effect was maximal at 0.1 nMPTH(1-34), the lowest concentration tested. The 3-34 amide analogue of PTH increased DG to the same extent as PTH(1-34). The effect was maximal at 10 nM PTH(3-34)amide, the lowest concentration tested. These concentrations were lower than those required to elicit maximal effects on bone resorption. In contrast to effects on cyclic AMP, where the 3-34 amide inhibited the increase elicited by PTH, combined treatment of calvaria with PTH(1-34) and PTH(3-34)amide did not inhibit effects on resorption or diacylglycerol.     

COVID-19 by numbers - infections,cases and deaths

During the COVID-19 pandemic, governments face difficult decisions when being confronted with public health threats and economic needs. Decision making is further complicated by the different perception of the pandemic by the public. Politicians as well as the public need objective facts for guidance and numbers play here a crucial role. The current contribution compiles numbers for infections, cases and deaths with SARS-CoV-2 to serve as an orientation help.     

Cholinergic regulation of fuel-induced hormone secretion and respiration of SUR1-/- mouse islets

Neural and endocrine factors (i.e., Ach and GLP-1) restore defective glucose-stimulated insulin release in pancreatic islets lacking sulfonylurea type 1 receptors (SUR1(-/-)) (Doliba NM, Qin W, Vatamaniuk MZ, Li C, Zelent D, Najafi H, Buettger CW, Collins HW, Carr RD, Magnuson MA, and Matschinsky FM. Am J Physiol Endocrinol Metab 286: E834-E843, 2004). The goal of the present study was to assess fuel-induced respiration in SUR1(-/-) islets and to correlate it with changes in intracellular Ca(2+), insulin, and glucagon secretion. By use of a method based on O(2) quenching of phosphorescence, the O(2) consumption rate (OCR) of isolated islets was measured online in a perifusion system. Basal insulin release (IR) was 7-10 times higher in SUR1(-/-) compared with control (CON) islets, but the OCR was comparable. The effect of high glucose (16.7 mM) on IR and OCR was markedly reduced in SUR1(-/-) islets compared with CON. Ach (0.5 microM) in the presence of 16.7 mM glucose caused a large burst of IR in CON and SUR1(-/-) islets with minor changes in OCR in both groups of islets. In SUR1(-/-) islets, high glucose failed to inhibit glucagon secretion during stimulation with amino acids or Ach. We conclude that 1) reduced glucose responsiveness of SUR1(-/-) islets may be in part due to impaired energetics, as evidenced by significant decrease in glucose-stimulated OCR; 2) elevated intracellular Ca(2+) levels may contribute to altered insulin and glucagon secretion in SUR1(-/-) islets; and 3) The amplitudes of the changes in OCR during glucose and Ach stimulation do not correlate with IR in normal and SUR1(-/-) islets suggesting that the energy requirements for exocytosis are minor compared with other ATP-consuming reactions.