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1.
This study aims to examine the inter-district and inter-village variation of utilization of health services for institutional births in EAG states in presence of rural health program and availability of infrastructures. District Level Household Survey-III (2007–08) data on delivery care and facility information was used for the purpose. Bivariate results examined the utilization pattern by states in presence of correlates of women related while a three-level hierarchical multilevel model illustrates the effect of accessibility, availability of health facility and community health program variables on the utilization of health services for institutional births. The study found a satisfactory improvement in state Rajasthan, Madhya Pradesh and Orissa, importantly, in Bihar and Uttaranchal. The study showed that increasing distance from health facility discouraged institutional births and there was a rapid decline of more than 50% for institutional delivery as the distance to public health facility exceeded 10 km. Additionally, skilled female health worker (ANM) and observed improved public health facility led to significantly increase the probability of utilization as compared to non-skilled ANM and not-improved health centers. Adequacy of essential equipment/laboratory services required for maternal care significantly encouraged deliveries at public health facility. District/village variables neighborhood poverty was negatively related to institutional delivery while higher education levels in the village and women’s residing in more urbanized districts increased the utilization. “Inter-district” variation was 14 percent whereas “between-villages” variation for the utilization was 11 percent variation once controlled for all the three-level variables in the model. This study suggests that the mere availability of health facilities is necessary but not sufficient condition to promote utilization until the quality of service is inadequate and inaccessible considering the inter-districts variation for the program implementation. 相似文献
2.
Laishram R. Singh Sapna Gupta Nicholaas H. Honig Jan P. Kraus Warren D. Kruger 《PLoS genetics》2010,6(1)
Missense mutant proteins, such as those produced in individuals with genetic diseases, are often misfolded and subject to processing by intracellular quality control systems. Previously, we have shown using a yeast system that enzymatic function could be restored to I278T cystathionine β-synthase (CBS), a cause of homocystinuria, by treatments that affect the intracellular chaperone environment. Here, we extend these studies and show that it is possible to restore significant levels of enzyme activity to 17 of 18 (94%) disease causing missense mutations in human cystathionine β-synthase (CBS) expressed in Saccharomyces cerevisiae by exposure to ethanol, proteasome inhibitors, or deletion of the Hsp26 small heat shock protein. All three of these treatments induce Hsp70, which is necessary but not sufficient for rescue. In addition to CBS, these same treatments can rescue disease-causing mutations in human p53 and the methylene tetrahydrofolate reductase gene. These findings do not appear restricted to S. cerevisiae, as proteasome inhibitors can restore significant CBS enzymatic activity to CBS alleles expressed in fibroblasts derived from homocystinuric patients and in a mouse model for homocystinuria that expresses human I278T CBS. These findings suggest that proteasome inhibitors and other Hsp70 inducing agents may be useful in the treatment of a variety of genetic diseases caused by missense mutations. 相似文献
3.
Radiomodulatory effect of liposome encapsulated AK-2123 on tumor in mice exposed to hepatocarcinogen 总被引:1,自引:0,他引:1
Alam A Rapthap CC Singha LI Sharan RN Singh V 《Molecular and cellular biochemistry》2005,271(1-2):139-150
An attempt was made to evaluate the whole body -radiation effect on tumor in the presence of free and liposome encapsulated AK-2123, a hypoxic cell radiosensitizer that has widely been used in combination with a number of cancer therapies such as thermotherapy, chemotherapy and radiotherapy. Entrapment efficiency of AK-2123 into liposome was determined by LASER Raman spectroscopy. Cancer induction in mice was carried out by repeated exposure of N-nitrosodiethylamine (DEN) in combination with partial hepatectomy. Parameters such as marker enzymes activities (GGT and AChE), rates of nucleic acid synthesis, viability modification factor and the histology of liver tissues monitored, supported the induction of cancer in liver. In addition, the effect of free as well as liposome encapsulated AK-2123 on haemopoietic parameters were also studied. It was observed that AK-2123 after incorporation into liposome afforded more efficient radiomodulatory effects than that of free AK-2123 as determined by the above-mentioned parameters. Neither free AK-2123 nor liposome encapsulated AK-2123 showed any detectable toxic effects on the mice. Thus, it is seen that treatment of cancer with a combination of radiation, a radiomodifier and a drug delivery system, opens a wide scope for exploitation for the improvement of existing cancer therapies. (Mol Cell Biochem 271: 139–150, 2005) 相似文献
4.
5.
Laishram Kosygin Bungdon Shangningam K. C. Gopi 《Environmental Biology of Fishes》2018,101(4):589-593
A new species, Olyra parviocula, is described from the Kameng River, Brahmaputra River drainage in Arunachal Pradesh, northeastern India. The new species differs from congeners in having small eye diameter 5–8% HL; short adipose fin, not confluent with caudal-fin, its base length 9–12% SL; dorsal-fin branched rays 6; anal-fin rays viii–xi, 8–10 and maxillary barbel almost reaching pelvic-fin base. A key to identification of all valid species of Olyra is provided. 相似文献
6.
Jummi Laishram Shripad Kondra Daniela Avossa Elisa Migliorini Marco Lazzarino Vincent Torre 《Journal of structural biology》2009,168(3):366-377
We have analyzed the morphology of growth cones of differentiating neurons from rat dorsal root ganglia (DRG) with conventional Laser Scanning Confocal Microscopy (LSCM) and Atomic Force Microscopy (AFM). Images of immunofluorescent DRG growth cones colabeled for actin and tubulin were superimposed to images obtained with AFM at different scanning forces. In order to reduce changes of the image surface caused by the pressure of the AFM tip, we have developed a procedure to obtain 0 pN AFM images. Further analysis of these images revealed topographical structures with nanoscale dimensions, referred to as “invaginations” or “holes”. These holes had an area varying from 0.01 to 3.5 μm2 with a depth varying from 2 to 178 nm. Comparative analysis with LSCM images showed that these holes correspond to regions where staining of both actin and tubulin was negligible. Filopodia height varied from 40 to 270 nm and their diameter from 113 to 887 nm. These results show that the combination of LSCM and AFM reveal structural details with a nanoscale dimension of DRG growth cones, difficult to resolve with conventional microscopy. 相似文献
7.
Many human diseases are caused by missense substitutions that result in
misfolded proteins that lack biological function. Here we express a mutant
form of the human cystathionine β-synthase protein, I278T, in
Saccharomyces cerevisiae and show that it is possible to dramatically
restore protein stability and enzymatic function by manipulation of the
cellular chaperone environment. We demonstrate that Hsp70 and Hsp26 bind
specifically to I278T but that these chaperones have opposite biological
effects. Ethanol treatment induces Hsp70 and causes increased activity and
steady-state levels of I278T. Deletion of the SSA2 gene, which
encodes a cytoplasmic isoform of Hsp70, eliminates the ability of ethanol to
restore function, indicating that Hsp70 plays a positive role in proper I278T
folding. In contrast, deletion of HSP26 results in increased I278T
protein and activity, whereas overexpression of Hsp26 results in reduced I278T
protein. The Hsp26-I278T complex is degraded via a
ubiquitin/proteosome-dependent mechanism. Based on these results we propose a
novel model in which the ratio of Hsp70 and Hsp26 determines whether misfolded
proteins will either be refolded or degraded.Cells have evolved quality control systems for misfolded proteins,
consisting of molecular chaperones (heat shock proteins) and proteases. These
molecules help prevent misfolding and aggregation by either promoting
refolding or by degrading misfolded protein molecules
(1). In eukaryotic cells, the
Hsp70 system plays a critical role in mediating protein folding. Hsp70 protein
interacts with misfolded polypeptides along with co-chaperones and promotes
refolding by repeated cycles of binding and release requiring the hydrolysis
of ATP (2). Small heat shock
proteins (sHsp)2 are
small molecular weight chaperones that bind non-native proteins in an
oligomeric complex and whose function is poorly understood
(3). In mammalian cells, the
sHsp family includes the α-crystallins, whose orthologue in
Saccharomyces cerevisiae is Hsp26. Studies suggest that Hsp26 binding
to misfolded protein aggregates is a prerequisite for effective disaggregation
and refolding by Hsp70 and Hsp104
(4,
5).Misfolded proteins can result from missense substitutions such as those
found in a variety of recessive genetic diseases, including cystathionine
β-synthase (CBS) deficiency. CBS is a key enzyme in the
trans-sulfuration pathway that converts homocysteine to cysteine
(6). Individuals with CBS
deficiency have extremely elevated levels of plasma total homocysteine,
resulting in a variety of symptoms, including dislocated lenses, osteoporosis,
mental retardation, and a greatly increased risk of thrombosis
(7). Approximately 80% of the
mutations found in CBS-deficient patients are point mutations that are
predicted to cause missense substitutions in the CBS protein
(8). The most common mutation
found in CBS-deficient patients, an isoleucine to threonine substitution at
amino acid position 278 (I278T), has been observed in nearly one-quarter of
all CBS-deficient patients. Based on the crystal structure of the catalytic
core of CBS, this mutation is located in a β-sheet more than 10 Å
distant from the catalytic pyridoxal phosphate and does not directly affect
the catalytic binding pocket or the dimer interface
(9).Previously, our lab has developed a yeast bioassay for human CBS
in which yeast expressing functional human CBS can grow in media lacking
cysteine, whereas yeast expressing mutant CBS cannot
(10). We have used this assay
to characterize the functional effects of many different CBS missense alleles,
including I278T (7,
11). However, an unexpected
finding was that it was possible to restore function to I278T and a number of
other CBS missense mutations by either truncation or the addition of a second
missense mutation in the C-terminal regulatory domain
(12,
13). The ability to restore
function by a cis-acting second mutation suggested to us that it
might be possible to restore function in trans via either interaction
of mutant CBS with a small molecule (i.e. drug) or a mutation in
another yeast gene. In a previous study, we found that small osmolyte chemical
chaperones could restore function to mutant CBS presumably by directly
stabilizing the mutant CBS protein
(14).In this study we report on the surprising finding that exposure of yeast to
ethanol can restore function of I278T CBS by altering the ratio of the
molecular chaperones Hsp26 and Hsp70. We demonstrate Hsp70 binding promotes
I278T folding and activity, whereas Hsp26 binding promotes I278T degradation
via the proteosome. By manipulating the levels of Hsp26 and Hsp70, we are able
to show that I278T CBS protein can have enzymatic activity restored to near
wild-type levels of activity. Our findings suggest a novel function for
sHsps. 相似文献
8.
Irom?Harimala?Chanu Laishram?Ronibala?Devi Nonibala?Khumanthem N.?Irabanta?Singh Dalip?Kumar Okram?Mukherjee?SinghEmail author 《Russian Journal of Bioorganic Chemistry》2017,43(2):177-185
Knoevenagel cyclocondensations of α-hydroxy naphthaldehyde with β-oxodithioesters and ketene dithioacetals yielded 2H-benzo[f]chromene-2-thiones and 2H-benzo[f]chromen-2-ones, respectively, in high yields. The newly synthesized compounds were evaluated for antifungal and antibacterial activities. Among them, compounds (2-furyl)(3-thioxo-3H-benzo[f]chromen-2-yl)methanone and phenyl(3-oxo-3H-benzo[f]chromen-2-yl)methanone exhibited excellent antifungal activity against tested fungi Curvularia lunata and Fusarium moniliforme. The highest antibacterial activity against the tested bacteria Escherichia coli and Staphylococcus aureus was observed for (4-chlorophenyl)(3-oxo-3H-benzo[f]chromen-2-yl)methanone. The results of antimicrobial screening demonstrate that (2-furyl)(3-thioxo-3H-benzo[f]chromen-2-yl)methanone, phenyl(3-oxo-3H-benzo[f]chromen-2-yl)methanone, and (4-chlorophenyl)(3-oxo-3H-benzo[f]chromen-2-yl)methanone are promising as antimicrobial drugs. 相似文献
9.
Osmolytes are naturally occurring small molecules accumulated intracellularly to protect organisms from various denaturing stresses. Similar to the two faces of a coin, several of these osmolytes are stabilizing and destabilizing proteins depending on the concentrations and/or solvent conditions. For example, the well known stabilizing osmolyte, trehalose destabilizes some proteins at high concentration and/or high pH. In spite of the fact that destabilizing aspects of osmolytes can modulate many cellular processes including regulation of protein homeostasis (proteostasis), protein-protein interaction, and protein-DNA interaction, researchers have mostly focused on the stabilizing aspects of osmolytes. Thus, it is important to look into both aspects of osmolytes to determine their precise role under physiological conditions. In this article, we have discussed both stabilizing and destabilizing/denaturant aspects of osmolytes to uncover both sides of the coin. 相似文献
10.
Marina Warepam Gurumayum Suraj Sharma Tanveer Ali Dar Md. Khurshid Alam Khan Laishram Rajendrakumar Singh 《PloS one》2014,9(10)
Osmolytes are low molecular weight organic molecules accumulated by organisms to assist proper protein folding, and to provide protection to the structural integrity of proteins under denaturing stress conditions. It is known that osmolyte-induced protein folding is brought by unfavorable interaction of osmolytes with the denatured/unfolded states. The interaction of osmolyte with the native state does not significantly contribute to the osmolyte-induced protein folding. We have therefore investigated if different denatured states of a protein (generated by different denaturing agents) interact differently with the osmolytes to induce protein folding. We observed that osmolyte-assisted refolding of protein obtained from heat-induced denatured state produces native molecules with higher enzyme activity than those initiated from GdmCl- or urea-induced denatured state indicating that the structural property of the initial denatured state during refolding by osmolytes determines the catalytic efficiency of the folded protein molecule. These conclusions have been reached from the systematic measurements of enzymatic kinetic parameters (K
m and k
cat), thermodynamic stability (T
m and ΔH
m) and secondary and tertiary structures of the folded native proteins obtained from refolding of various denatured states (due to heat-, urea- and GdmCl-induced denaturation) of RNase-A in the presence of various osmolytes. 相似文献