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Biotin Supplementation Ameliorates Murine Colitis by Preventing NF-κB Activation.
Background & aimsBiotin is a water-soluble vitamin that is indispensable for human health. Biotin deficiency can cause failure-to-thrive, immunodeficiency, alopecia, dermatitis, and conjunctivitis. We previously reported that biotin deficiency also can lead to severe colitis in mice, which is completely reversed with supplementation. Our aim in this study was to determine if high-dose biotin supplementation can provide a therapeutic benefit in a preclinical model for inflammatory bowel disease (IBD) and to identify the molecular mechanism by which this occurs.MethodsMice were challenged with dextran sodium sulfate to induce colitis and were treated with 1 mmol/L biotin to induce or maintain remission. Clinical response was monitored by the Disease Activity Index and fecal calprotectin levels. The colon tissue was investigated for histology, length, as well as expression of inflammatory cytokines (interleukin 6, tumor necrosis factor-α, interleukin 1β), intestinal permeability, tight junctions (zonula occludens-1 and claudin-2), and the transcription factor nuclear factor-κB (NF-κB).ResultsBiotin therapy led to delayed onset and severity of colitis as well as accelerated healing. There was improvement in the Disease Activity Index, fecal calprotectin levels, colon length, and histology. In addition, biotin-treated mice had reduced expression of inflammatory cytokines, reduced intestinal permeability, and reduced activation of NF-κB.ConclusionsOral supplementation with biotin provides benefit for maintenance and induction of remission in the dextran sodium sulfate preclinical model for IBD. Biotin does this by reducing the activation of NF-κB, which prevents the production of inflammatory cytokines and helps maintain the integrity of the intestinal barrier. Clinically, the NF-κB pathway is important in the development of IBD and this finding suggests that biotin may have therapeutic potential for patients with IBD
Складові антикризового потенціалу будівельних підприємств в динамічних умовах
The concept of "anti-crisis potential" of a construction company is defined. The structure of anti-crisis potential of a construction enterprise is investigated. The main problems of functioning of enterprises of the construction industry of Ukraine in the pre-crisis period and in the newest political and economic conditions of the country's integration into the EU are identified. The latest trends in the development of construction in terms of full or partial integration with EU markets are substantiated.Визначено поняття «антикризовий потенціал» будівельного підприємства. Досліджено структуру антикризового потенціалу будівельного підприємства. Визначено основні проблеми функціонування підприємств будівельної галузі України у докризовий період і в новітніх політико-економічних умовах інтеграції країни до ЄС. Обґрунтовано новітні тенденції на напрямки розвитку будівництва в умовах повної або часткової інтеграції із ринками ЄС
Distinguishing Modes of Eukaryotic Gradient Sensing
The behaviors of biological systems depend on complex networks of interactions between large numbers of components. The network of interactions that allows biological cells to detect and respond to external gradients of small molecules with directed movement is an example where many of the relevant components have been identified. This behavior, called chemotaxis, is essential for biological functions ranging from immune response in higher animals to the food gathering and social behavior of ameboid cells. Gradient sensing is the component of this behavior whereby cells transduce the spatio-temporal information in the external stimulus into an internal distribution of molecules that mediate the mechanical and morphological changes necessary for movement. Signaling by membrane lipids, in particular 3' phosphoinositides (3'PIs), is thought to play an important role in this transduction. Key features of the network of interactions that regulates the dynamics of these lipids are coupled positive feedbacks that might lead to response bifurcations and the involvement of molecules that translocate from the cytosol to the membrane, coupling responses at distant point on the cell surface. Both are likely to play important roles in amplifying cellular responses and shaping their qualitative features.
To better understand the network of interactions that regulates 3'PI dynamics in gradient sensing, we develop a computational model at an intermediate level of detail. To investigate how the qualitative features of cellular response depend on the structure of this network, we define four variants of our model by adjusting the effectiveness of the included feedback loops and the importance of translocating molecules in response amplification. Simulations of characteristic responses suggest that differences between our model variants are most evident at transitions between efficient gradient detection and failure. Based on these results, we propose criteria to distinguish between possible modes of gradient sensing in real cells, where many biochemical parameters may be unknown. We also identify constraints on parameters required for efficient gradient detection. Finally, our analysis suggests how a cell might transition between responsiveness and non-responsiveness, and between different modes of gradient sensing, by adjusting its biochemical parameters
Ekstrak Bawang Putih Bubuk Dengan Menggunakan Proses Spray Drying
Bawang putih banyak digunakan sebagai bumbu utama pada berbagai masakan karena aromanya yang khas. Aroma khas tersebut karena adanya komponen aktif (Allicin) pada bawang putih. Allicin juga berguna untuk daya anti kolesterol yang dapat mencegah penyakit jantung, tekanan darah tinggi dan lain sebagainya. Komponen Allicin bersifat volatil sehingga bila penanganannya salah maka dapat menyebabkan kerusakan. Untuk mengawetkan bawang putih yaitu dengan cara pengeringan. Salah satu proses yang dapat digunakan adalah spray drying karena proses ini membutuhkan waktu yang singkat. Proses spray drying adalah proses pengeringan dengan cara menyemprotkan fase cair menjadi butiran-butiran kecil kemudian mengontakkannya dengan udara panas sehingga menjadi bubuk. Umpan yang akan dikeringkan dapat berupa larutan ataupun suspensi dengan viskositas tertentu. Penelitian ini dilakukan percobaan pembuatan ekstrak bawang putih bubuk dengan variasi perbandingan massa bawang putih dengan pelarut air tertentu yang dimulai dari perbandingan 1:1, variasi konsentrasi maltodekstrin 0%, 10%, 20%, 30%, 40% dan 50%, serta variasi suhu udara masuk 160 oC, 170 oC, 180 oC dan 190 oC. Hal yang diamati adalah pengaruh konsentrasi maltodekstrin dan suhu udara masuk terhadap karakteristik ekstrak bawang putih bubuk yang dihasilkan. Karakteristik bubuk yang dianalisa meliputi kadar air, bulk density, wettability, solubility dan organoleptik. Dari hasil analisa diketahui bahwa dengan meningkatnya suhu udara inlet menyebabkan terjadinya penurunan kadar air. Begitu juga dengan meningkatnya suhu udara masuk menyebabkan terjadinya peningkatan bulk density, wettability dan solubility
Stochastic homogenization of the laser intensity to improve the irradiation uniformity of capsules directly driven by thousands laser beams
Illumination uniformity of a spherical capsule directly driven by laser beams has been assessed numerically. Laser facilities characterized by ND = 12, 20, 24, 32, 48 and 60 directions of irradiation with associated a single laser beam or a bundle of NB laser beams have been considered. The laser beam intensity profile is assumed super-Gaussian and the calculations take into account beam imperfections as power imbalance and pointing errors. The optimum laser intensity profile, which minimizes the root-mean-square deviation of the capsule illumination, depends on the values of the beam imperfections. Assuming that the NB beams are statistically independents is found that they provide a stochastic homogenization of the laser intensity associated to the whole bundle, reducing the errors associated to the whole bundle by the factor , which in turn improves the illumination uniformity of the capsule. Moreover, it is found that the uniformity of the irradiation is almost the same for all facilities and only depends on the total number of laser beams Ntot = ND × NB
MHC class II–restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell–mediated autoimmunity
Although plasmacytoid dendritic cells (pDCs) express major histocompatibility complex class II (MHCII) molecules, and can capture, process, and present antigens (Ags), direct demonstrations that they function as professional Ag-presenting cells (APCs) in vivo during ongoing immune responses remain lacking. We demonstrate that mice exhibiting a selective abrogation of MHCII expression by pDCs develop exacerbated experimental autoimmune encephalomyelitis (EAE) as a consequence of enhanced priming of encephalitogenic CD4+ T cell responses in secondary lymphoid tissues. After EAE induction, pDCs are recruited to lymph nodes and establish MHCII-dependent myelin-Ag–specific contacts with CD4+ T cells. These interactions promote the selective expansion of myelin-Ag–specific natural regulatory T cells that dampen the autoimmune T cell response. pDCs thus function as APCs during the course of EAE and confer a natural protection against autoimmune disease development that is mediated directly by their ability to present of Ags to CD4+ T cells in vivo
Nucleus-Electron Model for States Changing from a Liquid Metal to a Plasma and the Saha Equation
We extend the quantal hypernetted-chain (QHNC) method, which has been proved
to yield accurate results for liquid metals, to treat a partially ionized
plasma. In a plasma, the electrons change from a quantum to a classical fluid
gradually with increasing temperature; the QHNC method applied to the electron
gas is in fact able to provide the electron-electron correlation at arbitrary
temperature. As an illustrating example of this approach, we investigate how
liquid rubidium becomes a plasma by increasing the temperature from 0 to 30 eV
at a fixed normal ion-density . The electron-ion
radial distribution function (RDF) in liquid Rb has distinct inner-core and
outer-core parts. Even at a temperature of 1 eV, this clear distinction remains
as a characteristic of a liquid metal. At a temperature of 3 eV, this
distinction disappears, and rubidium becomes a plasma with the ionization 1.21.
The temperature variations of bound levels in each ion and the average
ionization are calculated in Rb plasmas at the same time. Using the
density-functional theory, we also derive the Saha equation applicable even to
a high-density plasma at low temperatures. The QHNC method provides a procedure
to solve this Saha equation with ease by using a recursive formula; the charge
population of differently ionized species are obtained in Rb plasmas at several
temperatures. In this way, it is shown that, with the atomic number as the only
input, the QHNC method produces the average ionization, the electron-ion and
ion-ion RDF's, and the charge population which are consistent with the atomic
structure of each ion for a partially ionized plasma.Comment: 28 pages(TeX) and 11 figures (PS
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