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Milieu interior

Ramon Guixà-González, José L Albasanz, Ismael Rodriguez-Espigares, Manuel Pastor, Ferran Sanz, Maria Martí-Solano, Moutusi Manna, Hector Martinez-Seara, Peter W Hildebrand, Mairena Martín, Jana Selent
Cholesterol is a key component of cell membranes with a proven modulatory role on the function and ligand-binding properties of G-protein-coupled receptors (GPCRs). Crystal structures of prototypical GPCRs such as the adenosine A2A receptor (A2AR) have confirmed that cholesterol finds stable binding sites at the receptor surface suggesting an allosteric role of this lipid. Here we combine experimental and computational approaches to show that cholesterol can spontaneously enter the A2AR-binding pocket from the membrane milieu using the same portal gate previously suggested for opsin ligands...
February 21, 2017: Nature Communications
Jean-Paul Lallès
Growing evidence suggests the implication of the gut microbiota in various facets of health and disease. In this review, the focus is put on microbiota-host molecular cross-talk at the gut epithelial level with special emphasis on two defense systems: intestinal alkaline phosphatase (IAP) and inducible heat shock proteins (iHSPs). Both IAP and iHSPs are induced by various microbial structural components (e.g. lipopolysaccharide, flagellin, CpG DNA motifs), metabolites (e.g. n-butyrate) or secreted signal molecules (e...
2016: Journal of Animal Science and Biotechnology
Qixian Chen, Ruogu Qi, Xiyi Chen, Xi Yang, Xing Huang, Haihua Xiao, Xinhuan Wang, Wenfei Dong
Nucleic acid-based therapy has emerged as a revolutionary methodology for treatment of the diseases related to protein dysfunction; however, lack of systemically applicable synthetic delivery systems limits its current usage in local applications, particularly for DNA-based therapy with regard to the poor bioavailability in the systemic administrations. To overcome this obstacle, we compiled multiple chemistry-based strategies into the manufacture of the gene delivery formulations to pursue improved tolerability of DNA to the enzymatic degradation in the biological milieu and prolonged retention in the systemic circulation...
September 21, 2016: ACS Applied Materials & Interfaces
Chin-Min Kimmy Ho, Tomasz Paciorek, Emily Abrash, Dominique C Bergmann
Signal transduction from a cell's surface to its interior requires dedicated signaling elements and a cellular environment conducive to signal propagation. Plant development, defense, and homeostasis rely on plasma membrane receptor-like kinases to perceive endogenous and environmental signals, but little is known about their immediate downstream targets and signaling modifiers. Using genetics, biochemistry, and live-cell imaging, we show that the VAP-RELATED SUPPRESSOR OF TMM (VST) family is required for ERECTA-mediated signaling in growth and cell-fate determination and reveal a role for ERECTA-LIKE2 in modulating signaling by its sister kinases...
August 22, 2016: Developmental Cell
Dechao Yuan, Zhu Chen, Yuchuan Zhou, Dongqin Xiao, Kang Liu, Xiaocong Xiang, Li Deng, Hua Dong, Gang Feng
STUDY DESIGN: Fabrication and characterization of a regenerative intervertebral disc (IVD) cartilaginous endplate (CEP) based on tissue culturing on biomimetic scaffolds. OBJECTIVE: To fabricate a regenerative CEP to support nutrients and metabolites exchange between IVD and the milieu interior. SUMMARY OF BACKGROUND DATA: CEP is the only pathway for most cells inside IVD to obtain nutrients and to eliminate metabolites. However, CEP usually fails at the same time when IVD degenerates...
March 2017: Spine
Jennifer L Stow, Nicholas D Condon
The surface of mammalian cells offers an interface between the cell interior and its surrounding milieu. As part of the innate immune system, macrophages have cell surface features optimised for probing and sampling as they patrol our tissues for pathogens, debris or dead cells. Their highly dynamic and constantly moving cell surface has extensions such as lamellipodia, filopodia and dorsal ruffles that help detect pathogens. Dorsal ruffles give rise to macropinosomes for rapid, high volume non-selective fluid sampling, receptor internalisation and plasma membrane turnover...
April 2016: Clinical & Translational Immunology
Saikat Biswas, Pramit Kumar Chowdhury
Protein dynamics in cells have been shown to be markedly different from that in dilute solutions because of the highly crowded cellular interior. The volume exclusion arising from the high concentration of macromolecules present can affect both equilibrium and kinetic processes involving protein conformational changes. While global changes in structure leading to modulations in the stability of the protein have been well-documented, local changes that can have a large bearing on the functional aspects of these biomolecules are rare to come across...
June 9, 2016: Journal of Physical Chemistry. B
Kelvin J A Davies
Homeostasis is a central pillar of modern Physiology. The term homeostasis was invented by Walter Bradford Cannon in an attempt to extend and codify the principle of 'milieu intérieur,' or a constant interior bodily environment, that had previously been postulated by Claude Bernard. Clearly, 'milieu intérieur' and homeostasis have served us well for over a century. Nevertheless, research on signal transduction systems that regulate gene expression, or that cause biochemical alterations to existing enzymes, in response to external and internal stimuli, makes it clear that biological systems are continuously making short-term adaptations both to set-points, and to the range of 'normal' capacity...
June 2016: Molecular Aspects of Medicine
O V Batishchev, L A Shilova, M V Kachala, V Y Tashkin, V S Sokolov, N V Fedorova, L A Baratova, D G Knyazev, J Zimmerberg, Y A Chizmadzhev
UNLABELLED: Influenza virus is taken up from a pH-neutral extracellular milieu into an endosome, whose contents then acidify, causing changes in the viral matrix protein (M1) that coats the inner monolayer of the viral lipid envelope. At a pH of ~6, M1 interacts with the viral ribonucleoprotein (RNP) in a putative priming stage; at this stage, the interactions of the M1 scaffold coating the lipid envelope are intact. The M1 coat disintegrates as acidification continues to a pH of ~5 to clear a physical path for the viral genome to transit from the viral interior to the cytoplasm...
October 14, 2015: Journal of Virology
Yichao Ren, Honggang Zhao, Baofeng Su, Eric Peatman, Chao Li
Fish are covered by a watery gel-mucus, mainly secreted by the goblet cells, serving as the physical and biochemical barrier between the external environment and the interior milieu, playing more important roles in fish that without scale. Despite the important roles of mucus in fish immunity, the knowledge of detailed molecular events happened during infection process is still limited. While most studies were focused on characterizing the protein and enzyme activities in the mucus following challenge, no studies have examined the gene expression profiles in fish mucus...
October 2015: Fish & Shellfish Immunology
Jia Liu, Qihua Yang, Can Li
Biocatalysis with immobilized enzymes as catalysts holds enormous promise in developing more efficient and sustainable processes for the synthesis of fine chemicals, chiral pharmaceuticals and biomass feedstocks. Despite the appealing potentials, nowadays the industrial-scale application of biocatalysts is still quite modest in comparison with that of traditional chemical catalysts. A critical issue is that the catalytic performance of enzymes, the sophisticated and vulnerable catalytic machineries, strongly depends on their intracellular working environment; however the working circumstances provided by the support matrix are radically different from those in cells...
September 18, 2015: Chemical Communications: Chem Comm
Myan Do, Samuel A Isaacson, Gerry McDermott, Mark A Le Gros, Carolyn A Larabell
We can learn much about cell function by imaging and quantifying sub-cellular structures, especially if this is done non-destructively without altering said structures. Soft X-ray tomography (SXT) is a high-resolution imaging technique for visualizing cells and their interior structure in 3D. A tomogram of the cell, reconstructed from a series of 2D projection images, can be easily segmented and analyzed. SXT has a very high specimen throughput compared to other high-resolution structure imaging modalities; for example, tomographic data for reconstructing an entire eukaryotic cell is acquired in a matter of minutes...
September 1, 2015: Archives of Biochemistry and Biophysics
Xiaohui Zhang, Vipen K Sawhney, Arthur R Davis
PREMISE OF THE STUDY: Many angiosperms produce nectar that entices pollinator visits. Each floral nectary tends to embody a singular form, such as the receptacular ring arising beneath the ovary in mint flowers (Lamiaceae). Exceptionally, the annular floral nectary in Salvia farinacea possesses modified stomata plus secretory trichomes. This first study of nectary ultrastructure within the largest genus of Lamiaceae examined this unusual condition. METHODS: Nectary anatomy, histochemistry, and ultrastructure were investigated from fresh and fixed material using light microscopy and scanning electron and transmission electron microscopy...
November 2014: American Journal of Botany
Zhen Li, Thusitha P Muhandiramlage, John P Keogh, Henry K Hall, Craig A Aspinwall
A porous phospholipid nanoshell (PPN) sensor functionalized with a specific aptamer sensor agent was prepared for rapid detection of Hg(2+) in human urine with minimal sample preparation. Aptamer sensors provide an important class of optical transducers that can be readily and reproducibly synthesized. A key limitation of aptamer sensors, and many other optical sensors, is the potential of biofouling or biodegradation when used in complex biological matrices such as serum or urine, particularly when high levels of nucleases are present...
January 2015: Analytical and Bioanalytical Chemistry
Keiichi Itoi, Ashraf Hossain Talukder, Toshimitsu Fuse, Takuji Kaneko, Ryo Ozawa, Takayuki Sato, Takuma Sugaya, Katsuya Uchida, Maya Yamazaki, Manabu Abe, Rie Natsume, Kenji Sakimura
Corticotropin-releasing factor (CRF) is the key regulator of the hypothalamic-pituitary-adrenal axis. CRF neurons cannot be distinguished morphologically from other neuroendocrine neurons in the paraventricular nucleus of the hypothalamus (PVH) without immunostaining. Thus, we generated a knock-in mouse that expresses modified yellow fluorescent protein (Venus) in CRF neurons (CRF-Venus), and yet its expression is driven by the CRF promoter and responds to changes in the interior milieu. In CRF-Venus, Venus-expressing neurons were distributed in brain regions harboring CRF neurons, including the PVH...
October 2014: Endocrinology
William B Monteith, Gary J Pielak
The intracellular milieu differs from the dilute conditions in which most biophysical and biochemical studies are performed. This difference has led both experimentalists and theoreticians to tackle the challenging task of understanding how the intracellular environment affects the properties of biopolymers. Despite a growing number of in-cell studies, there is a lack of quantitative, residue-level information about equilibrium thermodynamic protein stability under nonperturbing conditions. We report the use of NMR-detected hydrogen-deuterium exchange of quenched cell lysates to measure individual opening free energies of the 56-aa B1 domain of protein G (GB1) in living Escherichia coli cells without adding destabilizing cosolutes or heat...
August 5, 2014: Proceedings of the National Academy of Sciences of the United States of America
Sushil Chawla, Tarun Chaudhary, S Aggarwal, G D Maiti, Kulharsh Jaiswal, Jairam Yadav
The eyes are our window to the world and offer us an island of vision in the sea of darkness. Equally, the eyes are also a window to peep into what is going on in the milieu interior. Pregnancy is a natural state of physiological stress for the body. Each organ system of the body in a pregnant lady behaves at variation than in a non-pregnant state. A complex interplay exists between how the pregnancy affects the eye and how ocular physiology and pathology may lead to the modification of the management of pregnancy...
July 2013: Medical Journal, Armed Forces India
Kathleen Connellan, Mads Gaardboe, Damien Riggs, Clemence Due, Amanda Reinschmidt, Lauren Mustillo
OBJECTIVE: To present a comprehensive review of the research literature on the effects of the architectural designs of mental health facilities on the users. BACKGROUND: Using a team of cross-disciplinary researchers, this review builds upon previous reviews on general and geriatric healthcare design in order to focus on research undertaken for mental health care facility design. METHODS: Sources were gathered in 2010 and 2011. In 2010 a broad search was undertaken across health and architecture; in 2011, using keywords and 13 databases, researchers conducted a systematic search of peer reviewed literature addressing mental health care and architectural design published between 2005 to 2012, as well as a systematic search for academic theses for the period 2000 to 2012...
2013: HERD
G Foffi, A Pastore, F Piazza, P A Temussi
More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour...
August 2, 2013: Physical Biology
Santhosh R, Kemba Padu, Bipin Singh Th, M Birkumar Sharma, Th Sudhir Chandra Singh
Breast carcinoma is the commonest cancer among females in a majority of the Indian cities. The advances in the research and management have improved the breast cancer survival significantly in the past three decades globally. Adenocarcinoma is the commonest histological variant which arises from the ductal epithelia. The myoepithelial cells (ME) are the normal components of the breast parenchyma, which separate the ductal epithelia from the basement membrane and the stroma. The pure ME cell carcinoma is extremely rare and only 38 cases have been reported so far in the indexed literature...
June 2013: Journal of Clinical and Diagnostic Research: JCDR
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