CHMP5 controls bone turnover rates by dampening NF-κB activity in osteoclasts

Greenblatt, Matthew B.,Park, Kwang Hwan,Oh, Hwanhee,Kim, Jung-Min,Shin, Dong Yeon,Lee, Jae Myun,Lee, Jin Woo,Singh, Anju,Lee, Ki-young,Hu, Dorothy,Xiao, Changchun,Charles, Julia F.,Penninger, Josef M. The Rockefeller University Press 2015 The Journal of experimental medicine Vol.212 No.8

<▼1><P>Greenblatt et al. show that deletion of CHMP5 in osteoclasts leads to increased bone resorption coupled with exuberant osteoblast activity, resembling an early onset form of human Paget’s Disease of Bone</P></▼1><▼2><P>Physiological bone remodeling requires that bone formation by osteoblasts be tightly coupled to bone resorption by osteoclasts. However, relatively little is understood about how this coupling is regulated. Here, we demonstrate that modulation of NF-κB signaling in osteoclasts via a novel activity of charged multivesicular body protein 5 (CHMP5) is a key determinant of systemic rates of bone turnover. A conditional deletion of CHMP5 in osteoclasts leads to increased bone resorption by osteoclasts coupled with exuberant bone formation by osteoblasts, resembling an early onset, polyostotic form of human Paget’s disease of bone (PDB). These phenotypes are reversed by haploinsufficiency for <I>Rank</I>, as well as by antiresorptive treatments, including alendronate, zolendronate, and OPG-Fc. Accordingly, CHMP5-deficient osteoclasts display increased RANKL-induced NF-κB activation and osteoclast differentiation. Biochemical analysis demonstrated that CHMP5 cooperates with the PDB genetic risk factor valosin-containing protein (VCP/p97) to stabilize the inhibitor of NF-κBα (IκBα), down-regulating ubiquitination of IκBα via the deubiquitinating enzyme USP15. Thus, CHMP5 tunes NF-κB signaling downstream of RANK in osteoclasts to dampen osteoclast differentiation, osteoblast coupling and bone turnover rates, and disruption of CHMP5 activity results in a PDB-like skeletal disorder.</P></▼2>

Studies on Cocoon Filament Size Deviation in Multivoltine Breeds and Multivoltine ${\times}$ Bivoltine Hybrids of Silkworm, Bombyx mori L.

Rao, D.Raghavendra,Singh, Ravindra,Kariappa, B.K.,Dandin, S.B. Korean Society of Sericultural Science 2004 International Journal of Industrial Entomology Vol.9 No.2

Variation in the size of the silk filament will determine the uniformity and quality of the silk reeled. In the present study, an attempt has been made to study the filament size variation in 6 multivoltine parental breeds and 9 multivoltine ${\times}$ bivoltine hybrids in all three seasons of a year. All multivoltine breeds and multivoltine ${\times}$ bivoltine hybrids showed variation in filament size throughout its length from the outer layer to inner layer. Results of the present study indicated that the size of the filament decreased from outer to inner layer. The decrease in filament size was sudden in some breeds/hybrids whereas it was gradual in other. Relationship between filament length to that of slope, average filament size to slope, and maximum filament size to slope was determined based on regression analysis. Regression analysis revealed significant positive correlation between slope vs average filament length (r=0.92$^{**}$) in multivoltine${\times}$bivoltine hybrids. Among parental breeds, 96C showed lowest slope of the curve (b-value: -0.00428) and 96A showed highest slope of the curve (b-value: -0.00269). Among 9 hybrids, PM${\times}$N $B_4$ $D_2$ recorded lowest slope value (b-value: -0.00328) and BL24${\times}$N $B_4$ $D_2$ showed highest value for slope of the curve (b-value: -0.00234). The breed 96C, which showed lowest slope value can be utilized for future breeding programmes to breed strains with less size deviation. Three multivoltine${\times}$bivoltine hybrids viz., PM${\times}$N $B_4$ $D_2$, 96E${\times}$CSR19 and BL67${\times}$CS $R_{101}$ , which showed less slope values (b-values: -0.00328, -0.00300 and -0.00297 respectively) can be utilized for commercial exploitation to produce uniform silk.k.

Effect of Mechanical Alloying and Sintering Environment on the Crystallographic Evolution, Microstructure, Mechanical and Corrosion Properties of Porous Ti4Al4Co Alloy

Pradeep Singh,Vikas Shrivastava,I. B. Singh,D. P. Mondal 대한금속·재료학회 2022 METALS AND MATERIALS International Vol.28 No.6

Three group of porous Ti4Al4Co samples made of (i) unmilled powder and vacuum sintered (S1), (ii) milled powder andvacuum sintered (S2), and (iii) milled powder sintered in open atmosphere (S3) were prepared. Phase change, crystallite sizeand lattice strain variations due to powder milling and sintering were examined by SEM and XRD. To evaluate mechanicalproperty, alloy samples were subjected to the uniaxial compression test. For corrosion analysis, Tafel plot was plotted usingelectrochemical corrosion system in simulated body fluid (SBF) as electrolytic medium. From the obtained results, it wasfound that significant microstructural transformation takes place due to milling and change in sintering atmosphere. SampleS1possessed 139 MPa compressive strength, which was about 48% and 76% higher than samples S2and S3respectively. Corrosion current density for S3was found as 5.5 ± 0.3 μA/cm2 which is 7 and 12 times lower than S2and S1samples.

Correlation between defect structure and electrochemical properties of mixed conducting La_0.1Sr_0.9Co_0.8Fe_0.2O_3-δ

Choi, M.B.,Jeon, S.Y.,Singh, B.,Yoo, Y.S.,Hwang, J.H.,Song, S.J. Elsevier Science 2014 ACTA MATERIALIA Vol.65 No.-

The high catalytic properties of LSCF1982 arise from its defect structure. In this work, the oxygen nonstoichiometry (δ) of LSCF1982 was analyzed as a function of oxygen partial pressure (P<SUB>O'2</SUB>) and temperature for the -6≤log(P<SUB>O'2</SUB>/atm)≤0 and 800≤T/<SUP>o</SUP>C≤1000 ranges. A defect structure model for LSCF1982 was presented, which fitted well with the experimental data for δ. The equilibrium constants of appropriate defect reactions were determined. Analysis of the defect structure of LSCF1982 suggested that the conduction mechanism of LSCF1982 is governed by hopping conduction and band conduction of p-type carriers, which was determined by the analysis of thermoelectric power. The characteristic membrane thickness (L<SUB>c</SUB>), indicating the transition from predominantly bulk-diffusion controlled reaction to surface-exchange controlled reaction, had a value of 3.5+/-0.9x10<SUP>-2</SUP>cm. The oxygen vacancy diffusivity was calculated from the relationship between oxygen flux and oxygen chemical potential gradient. The chemical expansion was measured as a function of P<SUB>O'2</SUB> and temperature in the 10<SUP>-3</SUP>≤P<SUB>O'2</SUB>/atm≤0.21 and 800≤T/<SUP>o</SUP>C≤1000 ranges. The chemical expansion model based on the relative change in mean ionic radius was employed to compute the chemical expansion vs. δ, which indicated that the spin states of B-site transition metal ions are a mixture of high-spin and low-spin states, and made the transition from the low-spin to the high-spin state with an increase in δ and temperature.

Reliability analysis of a complex system, attended by two repairmen with vacation under marked process with the application of copula

N. Tiwari,S. B. Singh,M. Ram 한국신뢰성학회 2010 International Journal of Reliability and Applicati Vol.11 No.2

This paper deals with the reliability analysis of a complex system, which consists of two subsystems A and B connected in series. Subsystem A has only one unit and B has two units B1 and B2. Marked process has been applied to model the complex system. Present reliability model incorporated two repairmen: supervisor and novice to repair the failed units. Supervisor is always there and the novice remains in vacation and is called for repair as per demand. The repair rates for supervisor and novice follow general and exponential distributions respectively and the failure time for both the subsystems follows exponential distribution. The model is analyzed under “Head of line repair discipline”. By employing supplementary variable technique, Laplace transformation and Gumbel-Hougaard family of copula various transition state probabilities, reliability, availability and cost analysis have been obtained along with the steady state behaviour of the system. At the end some special cases of the system have been taken.

Frequency of group A rotavirus with mixed G and P genotypes in bovines: predominance of G3 genotype and its emergence in combination with G8/G10 types

Yashpal S. Malik,Kuldeep Sharma,Nirupama Vaid,Somendu Chakravarti,K. M. Chandrashekar,Sanjay S. Basera,Rashmi Singh,Minakshi,Gaya Prasad,Baldev R. Gulati,Kiren N. Bhilegaonkar,Awadh B. Pandey 대한수의학회 2012 JOURNAL OF VETERINARY SCIENCE Vol.13 No.3

The present study describes the genotypic distribution of rotaviruses (RVs) in an Indian bovine population with unexpectedly higher proportions of G3 alone or in combination of G8/G10. PCR-genotyping confirmed that 39.4% (13/33) of the prevalent RVs were the G3 type while 60.6% (20/33) were dual G3G10 or G3G8 types. P typing revealed that 93.9% (31/33) of the samples were P[11] while 6.1% (2/33) possessed a dual P[1]P[11] type. Sequence analysis of the VP7 gene from G3 strains viz. B-46, 0970, and BR-133 showed that these strains had sequence identities of 90.5% to 100% with other bovine G3 strains. The highest identity (98.9% to 100%) was observed with RUBV3 bovine G3 strains from eastern India. The G3 strains (B-46, 0970, and BR-133) showed 97.5% to 98.8% sequence homologies with the Indian equine RV strain Erv-80. Phylogenetic analysis demonstrated that G3 strains clustered with bovine RUBV3 and J-63, and equine Erv-80 G3. Overall, these results confirmed that the incidence of infection by RVs with the G3 genotype and mixed genotypes in the bovine population was higher than previously predicted. This finding reinforces the importance of constantly monitoring circulating viral strains with the G3 genotype in future surveillance studies.

Genomic Analyses of Toll-like Receptor 4 and 7 Exons of Bos indicus from Temperate Sub-himalayan Region of India

Malik, Y.P.S.,Chakravarti, S.,Sharma, K.,Vaid, N.,Rajak, K.K.,Balamurugan, V.,Biswas, S.K.,Mondal, B.,Kataria, R.S.,Singh, R.K. Asian Australasian Association of Animal Productio 2011 Animal Bioscience Vol.24 No.7

Toll-like receptors (TLRs) play an important role in the recognition of invading pathogens and the modulation of innate immune responses in mammals. The TLR4 and TLR7 are well known to recognize the bacterial lipopolysaccharide (LPS) and single stranded (ssRNA) ligands, respectively and play important role in host defense against Gram-negative bacteria and ssRNA viruses. In the present study, coding exon fragments of these two TLRs were identified, cloned, sequenced and analyzed in terms of insertion-deletion polymorphism, within bovine TLRs 4 and 7, thereby facilitating future TLR signaling and association studies relevant to bovine innate immunity. Comparative sequence analysis of TLR 4 exons revealed that this gene is more variable, particularly the coding frame (E3P1), while other parts showed percent identity of 95.7% to 100% at nucleotide and amino acid level, respectivley with other Bos indicus and Bos taurus breeds from different parts of the world. In comparison to TLR4, sequence analysis of TLR7 showed more conservation among different B. indicus and B. taurus breeds, except single point mutation at 324 nucleotide position (AAA to AAM) altering a single amino acid at 108 position (K to X). Percent identity of TLR7 sequences (all 3 exons) was between 99.2% to 100% at nucleotide and amino acid level, when compared with available sequence database of B. indicus and B. taurus. Simple Modular Architecture Research Tool (SMART) analysis showed variations in the exon fragments located in the Leucine Rich Repeat (LRR) region, which is responsible for binding with the microbial associated molecular patterns and further, downstream signaling to initiate anti-microbial response. Considering importance of TLR polymorphism in terms of innate immunity, further research is warranted.

Computational Tridimensional Protein Modeling of Cry1Ab19 Toxin from Bacillus thuringiensis BtX-2

( S. Kashyap ),( B. D. Singh ),( D. V. Amla ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.6

We report the computational structural simulation of the Cry1Ab19 toxin molecule from B. thuringiensis BtX-2 based on the structure of Cry1Aa1 deduced by x-ray diffraction. Validation results showed that 93.5% of modeled residues are folded in a favorable orientation with a total energy Z-score of -8.32, and the constructed model has an RMSD of only 1.13A. The major differences in the presented model are longer loop lengths and shortened sheet components. The overall result supports the hierarchical three-domain structural hypothesis of Cry toxins and will help in better understanding the structural variation within the Cry toxin family along with facilitating the design of domain-swapping experiments aimed at improving the toxicity of native toxins.

Charge and mass transport properties of La₂Ni_0.95Al_0.05O_4.025+δ

Jeon, S.Y.,Singh, B.,Im, H.N.,Seong, K.P.,Song, S.J. Elsevier Sequoia 2014 Journal of alloys and compounds Vol.589 No.-

<P>In this work, mass and charge transport properties of acceptor doped lanthanum nickelate, La2Ni0.95Al0.05O4.025+delta d (LNAO), were analyzed. The thermal expansion, electrical conductivity and thermoelectric power of LNAO were measured as a function of temperature in 25-1000 degrees C range and oxygen partial pressure ( pO(2)) in -14 <= log (pO(2)/atm)6 <= -1 range. The average thermal expansion coefficient was 13.77 x 10 (6) K (1). The electrical conductivity was analyzed in relation to the thermoelectric power to elucidate the positive deviation of the activity coefficient of hole on the basis of the delocalized electron model. The thermoelectric power measurement shows a p-type to n- type transition. The chemical diffusion coefficient (D-chem) and surface exchange coefficient (ksurf.) were calculated by 4-probe DC conductivity measurement and ksurf. was slightly higher than ((D) over tilde Dchem). The best- estimated hole-mobility values showed very weak temperature dependence. The results were compared with the literature results on La2NiO4+ d. (C) 2013 Elsevier B.V. All rights reserved.</P>

Mating Behaviour in Mulberry Silkworm, Bombyx mori (L.)

Saheb N. M. Biram,Singh Tribhuwan,Kalappa H. K.,Saratchandra B. Korean Society of Sericultural Science 2005 International Journal of Industrial Entomology Vol.10 No.2

Mating is an essential behavioural social event in the life cycle of silkworm, Bombyx mori (L.) for the perpetuation of population. A number of intrinsic and extrinsic factors and events of significant importance are involved in successful mating and egg deposition by an adult silk moth which besides biochemical, physiological and environmental factors also includes attraction of reproductively competent male and female moth for mating, duration and frequency of mating, age of moth at the time of mating, reuse of male moth in the production of eggs etc. An attempt has been made in this review article to elucidate briefly the behaviour of male towards female moth after eclosion, impact of duration and frequency of mating on egg deposition and oviposition, reuse of mated male moth in the production of quality and quantity eggs etc. in the silk-worm, B. mori and its significance in silkworm seed production.