Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue

Intrathecal pseudodelivery of drugs in the therapy of neurodegenerative diseases: rationale, basis and potential applications

Instituto de Salud Carlos III (ISCIII) [AC20/00017]; Agence Nationale de la Recherche (ANR); Unitatea Executiva Pentru Finantarea Invatamantului Superior a Cercetarii Dezvoltarii si Inovarii; Academy of Scientific Research and Technology (ASRT

Carboxymethyl guar gum nanoparticles for drug delivery applications: preparation and preliminary in-vitro investigations

Abstract Carboxymethyl guar gum (CMGG) synthesised from commercially available polysaccharide was formulated into nanoparticles via ionic gelation using trisodium trimetaphosphate (STMP) as cross-linking agent. Characterisation using a range of analytical techniques (FTIR, NMR, GPC, TGA and DLS) confirmed the CMGG structure and revealed the effect of the CMGG and STMP concentration on the main characteristics of the obtained nanoformulations. The average nanoparticle diameter was found to be around 208 nm, as determined by dynamic light scattering (DLS) and confirmed by scanning electron microscopy (SEM) and nanoparticle tracking analysis (NTA). Experiments using simulated gastric and intestinal fluids evidenced significant pH-dependent drug release behaviour of the nanoformulations loaded with Rhodamine B (RhB) as a model drug (loading capacity in excess of 83%), as monitored by UV-Vis. While dose-dependent cytotoxicity was observed, the nanoformulations appeared completely non-toxic at concentrations below 0.3 mg/mL. Results obtained so far suggest that carboxymethylated guar gum nanoparticles formulated with STMP warrant further investigations as polysaccharide based biocompatible drug nanocarriers

Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function

A wide variety of phytochemicals are consumed for their perceived health benefits. Many of these phytochemicals have been found to alter numerous cell functions, but the mechanisms underlying their biological activity tend to be poorly understood. Phenolic phytochemicals are particularly promiscuous modifiers of membrane protein function, suggesting that some of their actions may be due to a common, membrane bilayer-mediated mechanism. To test whether bilayer perturbation may underlie this diversity of actions, we examined five bioactive phenols reported to have medicinal value: capsaicin from chili peppers, curcumin from turmeric, EGCG from green tea, genistein from soybeans, and resveratrol from grapes. We find that each of these widely consumed phytochemicals alters lipid bilayer properties and the function of diverse membrane proteins. Molecular dynamics simulations show that these phytochemicals modify bilayer properties by localizing to the bilayer/solution interface. Bilayer-modifying propensity was verified using a gramicidin-based assay, and indiscriminate modulation of membrane protein function was demonstrated using four proteins: membrane-anchored metalloproteases, mechanosensitive ion channels, and voltage-dependent potassium and sodium channels. Each protein exhibited similar responses to multiple phytochemicals, consistent with a common, bilayer-mediated mechanism. Our results suggest that many effects of amphiphilic phytochemicals are due to cell membrane perturbations, rather than specific protein binding

Perancangan Sistem Communication-Based Train Control (CBTC) Berbasis Sensor Fusion

Meningkatnya jumlah penduduk, terutama di kota-kota besar dunia menyebabkan kebutuhan akan transportasi juga meningkat. Salah satu moda transportasi yang banyak dikembangkan untuk menjawab kebutuhan tersebut adalah kereta api. Communication-Based Train Control (CBTC) adalah salah satu pengembangan dari sistem pengoperasian kereta api yang menggunakan sistem blok bergerak. Pada sistem blok bergerak, jarak aman antar kereta api tidak lagi ditentukan oleh blok-blok rel dengan panjang yang tetap, melainkan berdasarkan kecepatan serta posisi dari kereta api yang beroperasi pada suatu rel. Dengan demikian jarak aman antar kereta api dapat diminimalkan. Pada penelitian ini, digunakan miniatur kereta api untuk merancang sistem CBTC. Sensor yang digunakan adalah enkoder, Indoor Positioning System (IPS), Radio Frequency Identification (RFID). Data posisi dan kecepatan dari ketiga sensor tersebut diolah menggunakan algoritma sensor fusion berbasis Unscented Kalman Filter (UKF) untuk mendapatkan data posisi kereta api yang lebih akurat. Estimasi posisi kemudian digunakan untuk merancang algoritma kontrol sinkronisasi pada blok bergerak. Dari penelitian ini diketahui bahwa algoritma UKF dapat menghasilkan estimasi posisi kereta api dengan baik sehingga algoritma kontrol sinkronisasi pada blok bergerak juga dapat diterapkan dengan baik