Directed differentiation of regulatory T cells from naive T cells and prevention of their inflammation-mediated instability using small molecules.

Regulatory T (Treg ) cell therapy is a promising approach for immune tolerance induction in autoimmunity conditions and cell/organ transplantations. Insufficient isolation yields and impurity during downstream processes and Treg instability after adoptive transfer in inflammatory conditions are major limitations to Treg therapy, and indicate the importance of seeking a valid, reliable method for de-novo generation of Tregs . In this research, we evaluated Treg -like cells obtained from different Treg differentiation protocols in terms of their yield, purity and activity. Differentiation was performed on naive CD4+ cells and a naive CD4+ /Treg co-culture by using three different protocols - ectopic expression of forkhead box protein P3 (E-FoxP3), soluble transforming growth factor ß (S-TGF) and small molecules [N-acetyl puromycin and SR1555 (N-Ac/SR)]. The results showed that a high yield of a homogeneous population of Treg -like cells could be achieved by the N-Ac/SR method under a T helper type 17 (Th17)-polarizing condition, particularly interleukin (IL)-6 and TGF-ß, when compared with the E-FoxP3 and S-TGF methods. Surprisingly, SR completely inhibited the differentiation of IL-17-producing cells and facilitated Treg generation in the inflammatory condition and had highly suppressive activity against T cell proliferation without Treg -specific demethylase region (TSDR) demethylation. For the first time, to our knowledge, we report the generation of efficient, pure Treg -like cells by using small molecules during in-vitro inflammatory conditions. Our results suggested that the N-Ac/SR method has several advantages for Treg generation when compared with the other methods, including a higher purity of Tregs , easier procedure, superior suppressive activity during the inflammatory condition and decreased cost.

Near-maximum microwave absorption in a thin metal film at the pseudo-free-standing limit.

Electromagnetic absorbers based on ultra-thin metallic film are desirable for many applications such as plasmonics, metamaterials, and long-wavelength detectors. A metallic film will achieve a maximum 50% of electromagnetic wave absorption, frequency independent, at a thickness defined by its conductivity, typically in the sub-Angstrom range for good metals if bulk conductivity is maintained throughout. This makes it extremely difficult to obtain substantial absorption from thin metal films, in contrast to 2D materials such as graphene. Luckily, however, from a practical point of view, metal conductivity is drastically reduced as the film becomes sub-100 nm, to make it a race between the thinnest possible metal thickness experimentally achievable vs the conductivity reduction. Here, we demonstrate a near-50% absorption at a gold film thickness of 6.5 nm, with conductivity much reduced from the bulk value, down to the range of 106 Siemens per meter. Studying the effect of the substrate thickness, we found that the common cover glass, with its thickness much smaller than the wavelength, achieves symmetric absorption of 44%, implying that a pseudo-free-standing limit is achieved. Our work may find applications in infrared sensing as in bolometers and biomedical sensing using microwaves.

Epidemiology of injuries and poisonings in emergency departments in Iran.

OBJECTIVES: There are few reports on epidemiological patterns of injury and injury-related mortality in developing countries. This study aimed to report the epidemiology of injuries and poisonings in emergency departments in Iran. STUDY DESIGN: Retrospective study using available data from 20 March 2005 to 19 March 2008. METHODS: Recorded Injury Surveillance System (ISS) data including demographics, place of residence, type of injury, and outcome during emergency department stay were extracted from the databank of the national ISS and included in the final analysis. RESULTS: In total, 2,991,624 emergency department admissions due to injury were recorded at university hospitals during the study period. According to the national census in 2006, Iran had a population of 70,472,846, so the injury admission rate to university hospital emergency departments was 1.4%/year in Iran. The mean age of the patients was 26.5 [standard deviation (SD) 16.9] years, and 72.7% of the cases were male. The most common cause of injury was road traffic accidents (RTAs) (31.9%), followed by hit (25.5%) and falls (10.9%). Intoxication was associated with 5.3% of all injuries. The overall emergency department mortality rate was 0.6%. Of those who died, the mean age was 32.6 (SD 21.1) years. All fatal injuries, except burn injuries, were more common in males. Intoxication-related deaths occurred in 3.8% of cases. In patients aged <13, 13-65 and >65 years, hit (28.2%), RTAs (34%) and RTAs (27.9%) were, respectively, the most common causes of injury. In all age groups, RTAs were the most common cause of death. CONCLUSIONS: This study determined the epidemiology of injuries and poisonings in emergency departments in Iran. The mortality rate in this study was low in comparison with other research, which may be explained in the context of inappropriate prehospital or interhospital care in Iran. This finding can be employed to formulate targeted preventive strategies based on the incidence of the more common types of injury.

Attenuation of neuromotor deficits by natural antioxidants of Decalepis hamiltonii in transgenic Drosophila model of Parkinson's disease.

Oxidative stress is believed to be a major factor for the onset of Parkinson's disease (PD). In this study, we have investigated oxidative status in transgenic Drosophila model of PD. Our results revealed elevated levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in A30P and A53T α-synuclein PD model flies compared to control. We have demonstrated for the first time the ameliorating potential of natural antioxidants characterized from the roots of Dh in A30P and A53T α-synuclein PD model flies. Feeding of transgenic flies with aqueous Dh root extract for 21 days significantly improved their climbing ability and circadian rhythm of locomotor activity which was associated with reduction in levels of ROS and LPO and enhancement in the activities of catalase (CAT) and superoxide dismutase (SOD). Dh protected against paraquat (PQ) sensitivity in α-synuclein transgenic flies and delayed the onset of PD-like symptoms which appears to be mediated by suppression of oxidative stress.

All-L-Leu-Pro-Leu-Pro: a challenging cyclization.

In this paper, we report the difficult synthesis of cyclo(Leu-Pro-Leu-Pro). While the cyclization of Leu-Pro-Leu-D-Pro did not cause problems, the all-L-peptide afforded cyclodimer rather than cyclotetrapeptide (cyclomonomer). A first attempt using our reversible backbone substitution methodology failed. However, we were successful in obtaining the desired cyclo(Leu-Pro-Leu-Pro) by decreasing the concentration. The ratio of cyclomonomer to cyclodimer was raised to 1:1.1 using BOP and 1:0.6 using HATU under our high dilution condition. The structures of the cyclopeptides were confidently assigned by electrospray ionization mass spectrometry and NMR.