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1.
So Jeong Park Doo Ri Park Deepak Bhattarai Kyeong Lee Jaesang Kim Yun Soo Bae Soo Young Lee 《Molecules and cells》2014,37(8):628-635
2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity. 相似文献
2.
Despite our extensive knowledge of insulin-like growth factor 1 (IGF1) action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs) derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate) from the bloodstream in a dose-dependent manner, the decline of IGF1 could be associated with the accumulation of glycation products and the decreasing resistance of bone to fracture. To test the aforementioned hypotheses, we used human tibial posterior cortex bone samples to perform biochemical (measurement of IGF1, fluorescent AGEs and pentosidine (PEN) contents) and mechanical tests (crack initiation and propagation using compact tension specimens). Our results for the first time show a significant, age-independent association between the levels of IGF1 and AGEs. Furthermore, AGEs (fAGEs, PEN) predict propensity of bone to fracture (initiation and propagation) independently of age in human cortical bone. Based on these results we propose a model of IGF1-based regulation of bone fracture. Because IGF1 level increases postnatally up to the juvenile developmental phase and decreases thereafter with aging, we propose that IGF1 may play a protective role in young skeleton and its age-related decline leads to bone fragility and an increased fracture risk. Our results may also have important implications for current understanding of osteoporosis- and diabetes-related bone fragility as well as in the development of new diagnostic tools to screen for fragile bones. 相似文献
3.
Vikas Yadav Patade Sujata Bhargava Penna Suprasanna 《Plant Cell, Tissue and Organ Culture》2012,108(2):279-286
In order to discriminate between the ionic and osmotic components of salt stress, sugarcane (Saccharum officinarum L. cv. Co 86032) calli were cultured on media containing NaCl or polyethylene glycol (PEG) 8000 that exerted the same osmotic
pressure (−0.7 MPa). PEG stress exposure for 15 days led to significant growth reduction and loss in water content than salt
stressed and control tissues. Osmotic adjustment (OA) was observed in callus tissues grown on salt, but was not evident in
callus grown on PEG. Oxidative damage to membranes, estimated in terms of accumulation of thiobarbituric acid reactive substances-TBARS
and electrolytic leakage was significantly higher in both the stressed calli than the control however, the extent of damage
was more in the PEG stressed calli. The stressed callus tissues showed inhibition of ascorbate peroxidase activity, while
catalase activity was increased. These results indicate sensitivity of cells to PEG-mediated stress than salt stress and differences
in their OA to these two stress conditions. The sensitivity to the osmotic stress indicate that expression of the stress tolerance
response requires the coordinated action of different tissues in a plant and hence was not expressed at the cellular level. 相似文献
4.
Rashi Verma Monika Yadav Rajabrata Bhuyan Shweta Aggarwal Arnab Nayek 《Journal of receptor and signal transduction research》2016,36(6):601-616
Computer-aided antibody engineering has been successful in the design of new biologics for disease diagnosis and therapeutic interventions. Interleukin-6 (IL-6), a well-recognized drug target for various autoimmune and inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and psoriasis, was investigated in silico to design potential lead antibodies. Here, crystal structure of IL-6 along with monoclonal antibody olokizumab was explored to predict antigen–antibody (Ag???Ab)-interacting residues using DiscoTope, Paratome, and PyMOL. Tyr56, Tyr103 in heavy chain and Gly30, Ile31 in light chain of olokizumab were mutated with residues Ser, Thr, Tyr, Trp, and Phe. A set of 899 mutant macromolecules were designed, and binding affinity of these macromolecules to IL-6 was evaluated through Ag???Ab docking (ZDOCK, ClusPro, and Rosetta server), binding free-energy calculations using Molecular Mechanics/Poisson Boltzman Surface Area (MM/PBSA) method, and interaction energy estimation. In comparison to olokizumab, eight newly designed theoretical antibodies demonstrated better result in all assessments. Therefore, these newly designed macromolecules were proposed as potential lead antibodies to serve as a therapeutics option for IL-6-mediated diseases. 相似文献
5.
For estimation of growth, the efficiency of linked cross sectional scheme has been compared with pure longitudinal and cross sectional schemes. The relevant estimation theory has been developed and the expressions for the optimum estimators alongwith their variances have been derived. It has been observed that for estimation of growth, the linked cross-sectional scheme has been observed to be less efficient as compared to pure longitudinal scheme but more efficient than pure cross-sectional scheme. 相似文献
6.
K.G. Raghu Richa Singh A. Prathapan Govind Kumar Yadav 《Chemico-biological interactions》2009,180(3):454-459
Haloperidol (HPL), well known antipsychotic drug can induce a marked QT prolongation and polymorphic arrhythmias. In this study we evaluated the influence of various induced risk factors such as electrolyte imbalance (hypokalemia and hypomagnesemia), gender difference, low pacing frequency, ischemia reperfusion insult on electrophysiological effect by haloperidol on electrically driven action potentials recorded from guinea pig papillary muscle. The doses of HPL ranging from 1 to 16 μM were used in this investigation. Action potentials (APs) were elicited electrically and recorded by classical microelectrode technique. HPL caused dose dependent prolongation of APD90 the final stage of repolarization, increased triangulation, and led into dispersion of action potential, conduction delay and conduction block. Magnitude of the effect of haloperidol was amplified significantly by most of the risk factors. Among the various risk factors, electrolyte imbalance (hypokalemia, hypomagnesemia) caused more amplification of HPL effect. Most of the risk factors amplified prolongation of APD90 by HPL. This effect is mainly due to the influence of these electrolytes and sex hormone on various ion channels involved in the repolarization phase of cardiac AP. This is the first report which provides an experimental evidence of amplification of electrophysiological effects of HPL in the presence of various risk factors. 相似文献
7.
R. R. Yadav 《Journal of biosciences》2009,34(5):699-707
Tree-ring analyses from semi-arid to arid regions in western Himalaya show immense potential for developing millennia long
climate records. Millennium and longer ring-width chronologies of Himalayan pencil juniper (Juniperus polycarpos), Himalayan pencil cedar (Cedrus deodara) and Chilgoza pine (Pinus gerardiana) have been developed from different sites in western Himalaya. Studies conducted so far on various conifer species indicate
strong precipitation signatures in ring-width measurement series. The paucity of weather records from stations close to tree-ring
sampling sites poses difficulty in calibrating tree-ring data against climate data especially precipitation for its strong
spatial variability in mountain regions. However, for the existence of strong coherence in temperature, even in data from
distant stations, more robust temperature reconstructions representing regional and hemispheric signatures have been developed.
Tree-ring records from the region indicate multi-century warm and cool anomalies consistent with the Medieval Warm Period
and Little Ice Age anomalies.
Significant relationships noted between mean premonsoon temperature over the western Himalaya and ENSO features endorse utility
of climate records from western Himalayan region in understanding long-term climate variability and attribution of anthropogenic
impact. 相似文献
8.
Intestinal iron absorption during suckling in mammals 总被引:1,自引:0,他引:1
The maintenance of appropriate iron levels is important for mammalian health, particularly during the rapid growth period
following birth. Too little iron can lead to irreversible damage to the developing central nervous system and too much iron
at this point can have adverse long term consequences, possibly due to excessive free radical production. In order to maintain
iron levels, intestinal iron absorption is very efficient in young mammals, such that almost all of the iron in breast milk
is utilized. However this high level of absorption is unable to be down regulated in response to excess iron as it can be
in adults, implying that different regulatory processes are involved during suckling. Various mechanisms have been proposed
to explain this high absorption, including enhanced expression of the proteins involved in iron absorption in adults (particularly
DMT1 and ferroportin), non-specific uptake via pinocytosis, and the uptake of lactoferrin bound iron by the lactoferrin receptor.
However, at present the precise mechanism is unclear. It is possible that all of these components contribute to the high intestinal
iron absorption seen during suckling, or a novel, as yet undescribed, mechanism could be involved. This review summarises
the evidence for and against each of the mechanisms described above and highlights how little is known about iron homeostasis
in this vital stage of development. 相似文献
9.
10.
Efficiency of linked cross-sectional scheme has been compared with pure longitudinal schemes for generalised estimation of norm relaxing the condition of constancy of variances. The relevant theory of estimation has been developed and the expression for the optimum estimators alongwith their variances have been derived. The percentage gain in efficiency has been calculated. It has been observed that for higher values of Q, percentage gain in efficiency of proposed scheme over cross-sectional is very high. 相似文献