Vacuumless kinks systems from vacuum ones, an example

Some years ago, Cho and Vilenkin, introduced a model which presents topological solutions, despite not having degenerate vacua as is usually expected. Here we present a new model with topological defects, connecting degenerate vacua but which in a certain limit recovers precisely the one proposed originally by Cho and Vilenkin. In other words, we found a kind of parent model for the so called vacuumless model. Then the idea is extended to a model recently introduced by Bazeia et al. Finally, we trace some comments the case of the Liouville model.Comment: 11 pages, 4 figure

Lactate, N-acetylaspartate, choline and creatine concentrations, and spin-spin relaxation in thalamic and occipito-parietal regions of developing human brain

Previous studies of the brains of normal infants demonstrated lower lactate (Lac)/choline (Cho), Lac/creatine (Cr), and Lac/ N-acetylaspartate (Naa) peak-area ratios in the thalamic region (predominantly gray matter) compared with occipitoparietal (mainly unmyelinated white matter) values. In the present study, thalamic Cho, Cr, and Naa concentrations between 32-42 weeks\u27 gestational plus postnatal age were greater than occipito-parietal: 4.6 +/- 0.8 (mean +/- SE), 10.5 +/- 2.0, and 9.0 +/- 0.7 versus 1.8 +/- 0.6, 5.8 +/- 1.5, and 3.4 +/- 1.1 mmol/kg wet weight, respectively: Lac concentrations were similar, 2.7 +/- 0.6 and 3.3 +/- 1.3 mmol/kg wet weight, respectively. In the thalamic region, Cho and Naa T2s increased, and Cho and Lac concentrations decreased, during development. Lower thalamic Lac peak-area ratios are principally due to higher thalamic concentrations of Cho, Cr, and Naa rather than less Lac. The high thalamic Cho concentration may relate to active myelination; the high thalamic Naa concentration may be due to advanced gray-matter development including active myelination. Lac concentration is higher in neonatal than in adult brain

Antinociceptive effects of acetyl met-enkephalin derivatives following intrathecal administration in rat

Introduction: Intrathecal infusion of some enkephalin derivatives has been shown to restore analgesia in morphine tolerant patients with less adverse effects such as respiratory depression and constipation compared to morphine. Therefore developing new enkephalin derivatives is of central interest in pain management. In this study, antinociceptive effects of intrathecal administration of two novel acetyl met-enkephalin analogues were evaluated compared to met-enkephalin. Methods and Results: To permit the intrathecal administration of drugs into the lumbar subarachnoid space in adult Wistar rats, polyethylene (PE10) catheters were implanted in the L2 and L3 spinal segments in anesthetized animals. After a recovery time of 4-5 days, to protect the drugs from biodegradation, all rats were pretreated with peptidase inhibitors (APC) including Amastatin (A), Phosphoramidon (P) and captopril (C). Animals were dosed with intrathecal infusion of the analogues followed by tail flick latency test for an hour. Acetyl-Met-enk-CHO and Acetyl-Met-enk did not show significant antinociceptive effects in 10 nM (10-8 M) concentration. However Acetyl-Met-enk-CHO described discernible effects in 100 nm (10-7 M) in comparison with enkephalin. To estimate resistance against peptidase, molecular modeling was performed and showed compound Acetyl-Met-enk-CHO has low affinity to active site of aminopeptidase, dipeptidylcarboxypeptidase-I and neutral endopeptidase; the degrading endogenous enkephalin opioid peptides. Conclusions: According to our results, Acethyl-Met-enk-CHO may provide comparable analgesic effects with, although with 10 folds less potency. With likely resistance against endogenous peptidase, this molecule could be a valuable lead compound for further studies

Antinociceptive effects of acetyl Leu-enkephalin derivatives following intrathecal administration in rat

Introduction: Intrathecal infusion of some enkephalin derivatives has been shown to restore analgesia in morphine tolerant patients with less adverse effects such as respiratory depression and constipation compared to morphine. Therefore developing new enkephalin derivatives is of central interest in pain management. In this study, antinociceptive effects of intrathecal administration of two novel acetyl met-enkephalin analogues were evaluated compared to met-enkephalin. Methods and Results: To permit the intrathecal administration of drugs into the lumbar subarachnoid space in adult wistar rats, polyethylene (PE10) catheters were implanted in the L2 and L3 spinal segments in anesthetized animals. After a recovery time of 4-5 days, to protect the drugs from biodegradation, all rats were pretreated with peptidase inhibitors (APC) including Amastatin, Phosphoramidon and captopril. Animals were dosed with intrathecal infusion of the analogues followed by tail flick latency test for an hour. Acetyl-Leu-enk-CHO and Acetyl-Leu-enk did not show any significant antinociceptive effects in 10 nM (10-8 M) concentration. However Acetyl-Leu-enk demonstrated considerable effects in 100 nm (10-7 M) compared to Leu-enkephalin. Surprisingly, Acetyl-Met-Leu-enk-CHO antinociception did not improve but decreased with increasing intrathecal dosage to 100 nm, probably working as a partial agonist on opioid receptors. Conclusions: According to our results, Acetyl-Leu-enk may provide better analgesic effects, compared to Acetyl-Leu-enk-CHO. With likely reverse dose-response effects on tail flick test, Acetyl-Leu-enk-CHO might be considered as a particular ligand for opioid receptors without full agonistic effect for further studies

Use of a biphasic perfusion process based on mild hypothermia for recombinant glucocerebrosidase (GBA) production

The main goal of this study was to develop an innovative CHO-based process for the production of glucocerebrosidase (GBA), an enzyme used for the replacement therapy of Type 1 Gaucher disease. The focus of the present study was on the development of a perfusion process, combining strategies that are commonly used for process optimization: temperature reduction, and supplementation of the culture medium with productivity enhancers, such as short chain fatty acids. The effects of mild hypothermic conditions combined with valeric acid supplementation were first studied in batch shake flasks for two clones (CHO-GBA-36K and CHO-GBA-65P), developed previously using as host the cell lines CHO.K1 (ATCC CCL-61) and CHO.PRO5 (a glycosylation mutant developed by Stanley et al. Cell 6:121, 1975), respectively. A DOE approach was used (Table 1) to select the most promising cultivation conditions to be further applied to a perfusion process. The best performance regarding both cell growth and GBA production was obtained for the CHO-GBA-65P clone under condition [1], at 31ºC with no valeric acid (Table 1). Under this condition, CHO-GBA-65P achieved a maximum qP of 58.4 mU/106 cells/d, which is 4.2 fold higher than qP at the control condition [2] and 2.7 fold higher than the maximum qP obtained for the CHO-GBA-36K clone, which was achieved at 31ºC with 2 mM valeric acid supplementation (condition [3]). Please click Additional Files below to see the full abstract

An addition of lithium chloride improves the transient gene expression yield in CHO cells

As hundreds of new recombinant therapeutic proteins enter into development each year, a cost-effective transient gene expression (TGE) system is required to assess these proteins at an early phase as a more rapid alternative to a stable gene expression system. While several strategies, such as genetic manipulation and environmental modification, have been attempted in TGE systems to improve the overall yield in Chinese hamster ovary (CHO) cells, chemical supplementation is often employed in industrial processes owing to its simplicity and effectiveness. Lithium chloride (LiCl), which is known to induce G2/M-phase cell cycle arrest, was found to be an attractive chemical additive to enhance recombinant protein production in CHO cells in a previous study by the authors. In the present study, we demonstrate that LiCl can be used as both a transfection facilitator and a production enhancer to enhance the TGE yield in CHO cells. In order to verify the effect of an addition of LiCl on transfection efficiency and episomal DNA stability in the TGE system, green fluorescent protein (GFP) was transiently transfected onto CHO cells in the absence or presence of LiCl and the fluorescence was measured by flow cytometry. At four hours post-transfection, the fluorescence signal was increased in a dose-dependent manner and was prolonged for 72 hours compared to non-added cultures, which showed weaker signals as time passed. For the TGE of monoclonal antibodies (mAb), an addition of 10mM LiCl along with DNA/PEI complexes also showed approximately a 1.3-fold increase in the final mAb concentration compared to non-added cultures. On the other hand, an addition of LiCl at various concentrations to four-hour post-transfected cultures increased the final mAb concentration to more than 3.5-fold compared to control cultures by inducing the G2/M-phase of cell cycle arrest. Taken together, the data obtained here demonstrate that LiCl is a potentially useful additive to improve TGE systems in CHO cells

Cobalamin inactivation induces formyltetrahydrofolate synthetase

AbstractLoss of cobalamin function produces profound changes in the metabolism of formate. There is impaired synthesis of formyltetrahydropteroylglutamate synthetase (CHO-H4,PteGlu), accumulation of endogenous formate and impaired utilization of [14C]formate. There are contradictory reports on the effect of cobalamin inactivation on CHO-H4PteGlu synthetase. This study confirms a significant increase in synthetase activity following cobalamin inactivation