Ultrasound bone mineral density of Os Calcis - its relationship with bone mineral markers and 25(OH) vitamin D in endemic fluorotic and non-fluorotic villages

Objectives: To study the relationship between the nutritional status, serum bone mineral markers, 25 hydroxy vitamin D [25(OH)D] levels and ultrasound bone mineral density (USBMD) of Os Calcis in subjects living in endemic fluorotic and non-fluorotic villages. Methods: Subjects from fluorotic (n=57) and non-fluorotic (n=79) villages were studied for their dietary habits, biochemical parameters of bone mineral markers, 25(OH)D levels and correlated with stiffness index (SI) measured using Achilles ultrasound bone densitometer. Results: Dietary calcium intake in both the villages is far below the recommended daily allowances (RDA) by Indian Council of Medical Research (ICMR), India for Indian population. The 25(OH)D correlated positively with energy intake (r=0.7; p<0.001); dietary calcium (r= 0.5; p<0.001); and negatively with phytate/calcium ratio (r=0.2; p<0.001), in subjects in fluorotic villages. No similar correlation was observed among subjects from non-fluorotic villages. For comparable levels of serum calcium, subjects in non-fluorotic villages were more osteopenic than the fluorotic counterparts. USBMD did not correlate with 25(OH)D in the fluorotic and non-fluorotic subjects. Conclusions: The dietary calcium intake among subjects from fluorotic and non-fluorotic villages is less than the RDA suggested by ICMR. The 25(OH)D levels of both these villages were in the vitamin D insufficiency range. USBMD does not correlate with the 25(OH)D status of an individual and it should not be used for screening osteoporosis in areas endemic for fluorosis

GC-MS analysis of yellow pigmented Macrococcus equipercicus isolated from alfalfa rhizosphere soil fields of Coimbatore

The rhizosphere of plant possesses important microflora, which secretes wide chemical compounds including secondary metabolites necessary for plant growth and development. The microbial flora of alfalfa plant rhizosphere soil region was explored for functional activity and we found upto ten different pigmented colonies. Due to good functional diversity, this yellow pigmented colony was taken for further studies. Thus, the culture was molecularly characterized and identified for potent bioactive components responsible for antimicrobial activity. The selected culture mass was cultured and secondary metabolites were produced and extracted using ethyl acetate and subjected to GC-MS analysis. The antimicrobial study revealed selective activity against Streptococcus pneumonia, and Proteus sp with zone of inhibition to be 18 and 20 mm respectively.&nbsp; Molecular identification of the isolate by 16S rRNA sequencing showed the isolate as Macrococcus equipercicus with 100 % similarity. Based on GC-MS analysis report 25bioactive compounds were identified and 13-docosenamide, hexadecanoic acid esters and quercetin were found in ethyl acetate extract. Conclusion: Thus the yellow pigmented gram positive cocci M.equipercicus isolated from Medicago sativa possessed wide antibacterial activity due to presence of quercetin. Through the studies, we were able to identify potent antibacterial compound producing bacteria from M. sativa plant rhizosphere soil

Photoluminescent and superparamagnetic reduced graphene oxide-iron oxide quantum dots for dual-modality imaging, drug delivery and photothermal therapy

Reduced graphene oxide–iron oxide quantum dots (QDs) with intrinsic photoluminescent and superparamagnetic properties were synthesized through a green, hydrothermal method that simultaneously reduced and shattered graphene nanosheets to form the dots. The structure, morphology, properties and cell viability of these QDs were investigated. The QDs emitted violet light when excited at 320 nm, possessed no residual magnetization upon magnetic hysteresis tests, and had low cytotoxicity to healthy cells at low concentrations. The suitability of the QDs for fluorescent and magnetic resonance dual-modality imaging was shown by in vitro imaging with dermal fibroblast cells and T2 relaxation time. A drug could be loaded onto the surface of the QDs, with a loading ratio of drug to QD of 0.31:1. The drug achieved a steady but full release from the QDs over 8 h: these drug-loaded QDs could be manipulated by an external magnetic stimulation for targeted drug delivery. The potential for use as a cancer photothermal therapy was demonstrated by both a rapid, ∼50 °C temperature increase by a suspension of 100 μg ml−1 of QDs and the photothermal ablation of HeLa cells in vitro under near infrared irradiation. The stability of the MGQDs in fetal calf serum was shown to improve when an ionic drug was coated on the surface

Chemistry of Triple-Decker Sandwich Complexes Containing Four-Membered Open B2E2 Rings (E = S or Se)

International audienceBuilding upon our earlier studies of cobaltaheteroboranes, we explore the chemistry with heavier group 9 metals. Reaction of [Cp*M(µ-Cl)Clx]2 (Cp* = η5-C5Me5; M = Co, x = 0; M = Rh or Ir, x = 1) with [LiBH4·THF], followed by thermolysis with an excess of chalcogen powders (S or Se), affords dimetallaheteroboranes nido-[(Cp*M)2B2H2E2], 1–4 (1 E = S; 2 E = Se, M = Co; 3 and 4 E = Se, M = Rh and Ir, respectively) in moderate-to-good yields. The solid-state structures of these compounds show open-cage triple-decker clusters. Attempts to isolate the Te analogue have failed; however, in the case of cobalt, we have isolated an 11 skeletal-electron-pair nido-[(Cp*Co)2B5H5Te2], 5. The X-ray diffraction structure of 5 shows monocapped square antiprismatic geometry, with two Te atoms in the core. To close the central four-membered B2E2 open ring of nido-1 and nido-2, we have performed a reaction with [Ru3(CO)12], which leads to the formation of closo-[(Cp*Co){µ-η5η5-B2H2E2M}M{µ-Ru(CO)4}], 6 and 7 [6 E = S; 7 E = Se; M = Ru(CO)2]. In contrast, the reactions of nido-2 and nido-3 with [Fe2(CO)9] result in heterometallic clusters nido-[(Cp*M)Fe(CO)3B2H2Se2], 8 and 9 (8 M = Co; 9 M = Rh), [(Cp*Co)Fe3(CO)8Se2], 10, and [(Cp*Co)Fe2(CO)7Se], 11. As nido-8 also contains a four-membered open ring B2Se2, we have treated this with [Ru3(CO)12], which yields closo-[(Cp*Co){µ-η5η5-B2H2Se2M}M{µ-Fe(CO)4}], 12 [M = Ru(CO)2], which is analogous to that of 7. In addition, we have analyzed the divergence in the reactivity of nido-[(Cp*M)2B2H2E2], 2–4, with the help of density functional theory calculations

Reactivity of cyclopentadienyl transition metal(II) complexes with borate ligands: Structural characterization of the toluene-activated molybdenum complex [Cp∗Mo(CO)2(η3-CH2C6H5)]

International audienceReactions of cyclopentadienyl transition-metal halide complexes [Cp*Mo(CO)Cl], 1, and [CpFe(CO)I], 2, (Cp = CH; Cp* = η-CMe) with borate ligands are reported. Treatment of 1 with [NaBt] (Bt = dihydrobis(2-mercapto-benzothiazolyl)borate) in toluene yielded [Cp*Mo(CO)(CHSN)], 3, and [Cp*Mo(CO)(η-CHCH)], 4, with a selective binding of toluene through C-H activation followed by orthometallation. Note that compound 4 is a structurally characterized toluene-activated molecule in which the metal is in η-coordination mode. Under similar reaction conditions, [NaPy] (Py = dihydrobis(2-mercaptopyridyl)borate) produced only the mercaptopyridyl molybdenum complex [Cp*Mo(CO)(CHSN)], 5, in good yield. On the other hand, when compound 2 was treated individually with [NaBt] (Bt = trihydro(2-mercapto-benzothiazolyl)borate) and [NaPy] in THF, formation of the η-coordinated complexes [CpFe(CO)(CHSN)], 6, and [CpFe(CO)(CHSN)], 7, was observed. The solid-state molecular structures of compounds 3, 4, 6, and 7 have been established by single-crystal X-ray crystallographic analyses

SCREENING OF NOVEL AMINOPYRIMIDINE DERIVATIVES AGAINST HUMAN CDK-8 ENZYME: AN INSILICO APPROACH

The Human CDK8-CYCC in complex with compound 4: N-methyl-4-(4-pyridyl)-1H-pyrrole-2-carboxamide (PDB ID: 5XQX) was obtained from Protein Data Bank . These aminopyrimidine compounds are designed insilico with help of Chemsketch. The molecular docking study was performed using AutoDock vina software. The active binding site of the compounds were screened in the Biovia-2019.ds2019client. The pharmacokinetics and physiochemical properties were calculated in SwissADME. The toxicity of the compound is studied by using PreADME and PreTox-Ⅱ Prediction software.The designed compounds shows a better binding affinity than the standard drug 5-fluro uracil and based on the toxicity studies performed , the compounds are non-toxic in nature. &nbsp;This study leads to the development of novel aminopyrimidine derivatives as anticancer agent against Human cyclic dependent kinase (CDK-8) enzyme

Improving the Odds of Success in Drug Discovery: Choosing the Best Compounds for in Vivo Toxicology Studies

A set of molecules that advanced into exploratory animal toxicology studies (two species) was examined to determine what properties contributed to success in these safety studies. Compounds were rigorously evaluated across numerous safety end points and classified as “pass” if a suitable in vivo therapeutic index (TI) was achieved for advancement into regulatory toxicology studies. The most predictive end point contributing to compound survival was a predicted human efficacious concentration (<i>C</i>_eff) of ≤250 nM (total drug) and ≤40 nM (free drug). This trend held across a wide range of CNS modes of action, encompassing targets such as enzymes, G-protein-coupled receptors, ion channels, and transporters

Histone Acetylome-wide Association Study of Autism Spectrum Disorder.

The association of histone modification changes with autism spectrum disorder (ASD) has not been systematically examined. We conducted a histone acetylome-wide association study (HAWAS) by performing H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) on 257 postmortem samples from ASD and matched control brains. Despite etiological heterogeneity, ≥68% of syndromic and idiopathic ASD cases shared a common acetylome signature at &gt;5,000 cis-regulatory elements in prefrontal and temporal cortex. Similarly, multiple genes associated with rare genetic mutations in ASD showed common "epimutations." Acetylome aberrations in ASD were not attributable to genetic differentiation at cis-SNPs and highlighted genes involved in synaptic transmission, ion transport, epilepsy, behavioral abnormality, chemokinesis, histone deacetylation, and immunity. By correlating histone acetylation with genotype, we discovered &gt;2,000 histone acetylation quantitative trait loci (haQTLs) in human brain regions, including four candidate causal variants for psychiatric diseases. Due to the relative stability of histone modifications postmortem, we anticipate that the HAWAS approach will be applicable to multiple diseases