Molecular Weight Dependence of Exciton Diffusion in Poly(3‐hexylthiophene)

A joint experimental and theoretical study of singlet exciton diffusion in spin‐coated poly(3‐hexylthiophene) (P3HT) films and its dependence on molecular weight is presented. The results show that exciton diffusion is fast along the co‐facial π–π aggregates of polymer chromophores and about 100 times slower in the lateral direction between aggregates. Exciton hopping between aggregates is found to show a subtle dependence on interchain coupling, aggregate size, and Boltzmann statistics. Additionally, a clear correlation is observed between the effective exciton diffusion coefficient, the degree of aggregation of chromophores, and exciton delocalization along the polymer chain, which suggests that exciton diffusion length can be enhanced by tailored synthesis and processing conditions.     

Low Dose Infliximab for Prevention of Postoperative Recurrence of Crohn’s Disease: Long Term Follow-Up and Impact of Infliximab Trough Levels and Antibodies to Infliximab

Objective

In patients with postoperative recurrence of Crohn’s disease endoscopic and clinical remission can be maintained for up to 1 year with low infliximab doses (3 mg/Kg). However, in theory low-dose infliximab treated patients could develop subtherapeutic trough levels, infiximab antibodies, and might loose response to therapy. To verify this hypothesis infliximab pharmacokinetics and clinical/endoscopic response were checked in a group of patients treated in the long term with low infliximab doses.

Design

Infliximab antibodies, infliximab levels, highly-sensitive CRP and fecal calprotectin were measured during the 8-week interval in 5 consecutive patients in clinical (Crohn’s Disease Activity Index < 150) and endoscopic (Rutgeerts scores 0–1) remission after one year of therapy with infliximab 3 mg/Kg. For comparison with reported standards, infliximab pharmacokinetics and inflammatory parameters were also tested in 6 Crohn’s disease patients who did not undergo surgery and who were in clinical remission while on infliximab 5 mg/Kg. Patients on low infliximab dose also underwent colonoscopy after 18 additional months of therapy.

Results

Highly sensitive CRP and fecal calprotectin increased in all patients during the 8-week interval. Infliximab trough levels were lower in patients treated with the low dose compared to controls (mean±SE: 2.0±0.3 vs 4.75±0.83 μg/mL respectively p<0.05). Infliximab antibodies were present in two of the subjects treated with low infliximab dose and in none of the controls. However, in low dose-treated patients after 18 additional months of therapy endoscopy continued to show mucosal remission and none of them developed clinical recurrence or side effects.

Conclusions

Patients treated with low infliximab doses had lower trough levels compared to patients treated with 5 mg/Kg and some developed antibodies to infliximab. However, low infliximab doses sustained clinical and endoscopic remission for a total of 30 months of treatment.     

The effects of a loin muscling quantitative trait locus (LoinMAX™) on carcass and VIA-based traits in crossbred lambs

LoinMAX (LM) is a quantitative trait locus (QTL), which was found to be segregated in Australian Poll Dorset sheep, and maps to the distal end of sheep chromosome 18. LM-QTL was reported to increase Musculus longissimus dorsi area and weight by 11% and 8%, respectively. The aim of this study was to comprehensively evaluate the direct effects of LM-QTL in a genetic background typical of the stratified structure of the UK sheep industry, before it can be recommended for use in the United Kingdom. Crossbred lambs, either non-carriers or carrying a single copy of LM-QTL, were produced out of Scottish Mule ewes (Bluefaced Leicester × Scottish Blackface) artificially inseminated with semen from two Poll Dorset rams that were heterozygous for LM-QTL. Unexpectedly, one of these rams was also heterozygous for a QTL that affects the overall carcass muscling (MyoMAX™). This was accounted for by nesting MyoMAX™ status (carrier or non-carrier) within sire in the statistical analysis. Lambs were weighed and scanned by using X-ray computed tomography (CT) at an average age of 113 days. Ultrasound scan measurements, along with lamb weights, were taken at an average age of 140 days and lambs were then slaughtered. Carcasses were weighed and classified for fat cover and conformation scores, based on the Meat and Livestock Commission (MLC) carcass classification scheme, and then scanned by using a video image analysis (VIA) system. M. longissimus lumborum (MLL) width, as measured by CT scanning, was greater (P < 0.05) in lambs heterozygous for LM-QTL compared with non-carriers. MLL in LM-QTL carrier lambs was also significantly deeper, as measured by both ultrasound muscle depth at the third lumbar vertebrae (+3.7%; P < 0.05) and CT scanning at the fifth lumbar vertebrae (+3.4%; P < 0.01). Consequently, MLL area, was measured by using CT scanning, was significantly higher (+4.5%; P < 0.01) in lambs carrying a single copy of LM-QTL compared with non-carriers. Additional traits measured by CT, such as leg muscle dimensions, average muscle density and tissue proportions, were not significantly affected by LM-QTL. LM-QTL did not significantly affect total carcass lean or fat weights or MLC conformation and fat score classifications. Using previously derived algorithms, VIA could detect a significant effect of the LM-QTL on the predicted weight of saleable meat yield in the loin primal cut (+2.2%; P < 0.05), but not in the other primal cuts, or the total carcass.     

Dendritic cell function can be modulated through cooperative actions of TLR ligands and invariant NKT cells

The quality of signals received by dendritic cells (DC) in response to pathogens influences the nature of the adaptive response. We show that pathogen-derived signals to DC mediated via TLRs can be modulated by activated invariant NKT (iNKT) cells. DC maturation induced in vivo with any one of a variety of TLR ligands was greatly improved through simultaneous administration of the iNKT cell ligand alpha-galactosylceramide. DC isolated from animals treated simultaneously with TLR and iNKT cell ligands were potent stimulators of naive T cells in vitro compared with DC from animals treated with the ligands individually. Injection of protein Ags with both stimuli resulted in significantly improved T cell and Ab responses to coadministered protein Ags over TLR stimulation alone. Ag-specific CD8(+) T cell responses induced in the presence of the TLR4 ligand monophosphoryl lipid A and alpha-galactosylceramide showed faster proliferation kinetics, and increased effector function, than those induced with either ligand alone. Human DC exposed to TLR ligands and activated iNKT cells in vitro had enhanced expression of maturation markers, suggesting that a cooperative action of TLR ligands and iNKT cells on DC function is a generalizable phenomenon across species. These studies highlight the potential for manipulating the interactions between TLR ligands and iNKT cell activation in the design of effective vaccine adjuvants.     

Apelin signalling: a promising pathway from cloning to pharmacology

The discovery of new signalling pathways is always followed by the development of pharmacological agents as drugs that can be used in the treatment of diseases resulting from a dysfunction of the signalling pathway in question. Apelin signalling plays a role in the central and peripheral regulation of the cardiovascular system, in water and food intake, and possibly in immune function. Up-regulation of ligand and receptor is also associated with pathophysiological states such as cardiac dysfunction and neovascularisation. Finally, the apelin receptor is a coreceptor for the entry of several HIV-1 and SIV strains. In view of these features, the apelin receptor constitutes a very interesting target for the design of new drugs for treating the prime causes of human mortality.