A multicentre, retrospective case-control study assessing the role of trabecular bone score (TBS) in menopausal Caucasian women with low areal bone mineral density (BMDa): Analysing the odds of vertebral fracture.

INTRODUCTION: The trabecular bone score (TBS) is a new parameter that is determined from grey level analysis of DXA images. It relies on the mean thickness and volume fraction of trabecular bone microarchitecture. This was a preliminary case-control study to evaluate the potential diagnostic value of TBS, both alone and combined with bone mineral density (BMDa), in the assessment of vertebral fracture. METHODS: Out of a subject pool of 441 Caucasian, postmenopausal women between the ages of 50 and 80 years, we identified 42 women with osteoporosis-related vertebral fractures, and compared them with 126 age-matched women without any fractures (1 case: 3 controls). Primary outcomes were BMDa and TBS. Inter-group comparisons were undertaken using Student's t-tests and Wilcoxon signed ranks tests for parametric and non-parametric data, respectively. Odds ratios for vertebral fracture were calculated for each incremental one standard deviation decrease in BMDa and TBS, and areas under the receiver operating curve (AUC) calculated and sensitivity analysis were conducted to compare BMDa alone, TBS alone, and the combination of BMDa and TBS. Subgroup analyses were performed specifically for women with osteopenia, and for women with T-score-defined osteoporosis. RESULTS: Across all subjects (n=42, 126) weight and body mass index were greater and BMDa and TBS both less in women with fractures. The odds of vertebral fracture were 3.20 (95% CI, 2.01-5.08) for each incremental decrease in TBS, 1.95 (1.34-2.84) for BMDa, and 3.62 (2.32-5.65) for BMDa + TBS combined. The AUC was greater for TBS than for BMDa (0.746 vs. 0.662, p=0.011). At iso-specificity (61.9%) or iso-sensitivity (61.9%) for both BMDa and TBS, TBS + BMDa sensitivity or specificity was 19.1% or 16.7% greater than for either BMDa or TBS alone. Among subjects with osteoporosis (n=11, 40) both BMDa (p=0.0008) and TBS (p=0.0001) were lower in subjects with fractures, and both OR and AUC (p=0.013) for BMDa + TBS were greater than for BMDa alone (OR=4.04 [2.35-6.92] vs. 2.43 [1.49-3.95]; AUC=0.835 [0.755-0.897] vs. 0.718 [0.627-0.797], p=0.013). Among subjects with osteopenia, TBS was lower in women with fractures (p=0.0296), but BMDa was not (p=0.75). Similarly, the OR for TBS was statistically greater than 1.00 (2.82, 1.27-6.26), but not for BMDa (1.12, 0.56-2.22), as was the AUC (p=0.035), but there was no statistical difference in specificity (p=0.357) or sensitivity (p=0.678). CONCLUSIONS: The trabecular bone score warrants further study as to whether it has any clinical application in osteoporosis detection and the evaluation of fracture risk.

Rendimiento y composición mineral del forraje de una pradera permanente fertilizada con magnesio

Como una alternativa de manejo agronómico de la hipomagnesemia en rebaños a pastoreo se estudió, durante dos años, el efecto de la fertilización magnésica (0, 24, 48 y 96 kg ha-1 año-1 de Mg) sobre la concentración de magnesio, calcio, potasio y sodio y sus relaciones en la materia seca del forraje cosechado de una pradera permanente compuesta por Lolium perenne y Trifolium repens. El ensayo se realizó en un suelo Hapludand (Serie Valdivia) con un nivel inicial de 0,8 cmol c kg-1 de Mg. No se detectó un efecto de la fertilización magnésica sobre la producción de materia seca de la pradera, pero la concentración de magnesio en la materia seca se incrementó proporcionalmente a la dosis de magnesio aplicada. Considerando el promedio ponderado anual el aumento de la concentración de magnesio fue de 0,006 y 0,012 g kg-1 de materia seca por cada kg de magnesio aplicado, durante el primero y segundo año, respectivamente. La fertilización magnésica disminuyó la concentración de calcio, pero no afectó la concentración de potasio ni de sodio en la materia seca del forraje cosechado. Las relaciones entre Ca/Mg, K/Mg y Na/Mg en general disminuyeron en la medida que aumentó la dosis de fertilización con magnesio.

The glucose transporter 4 FQQI motif is necessary for Akt Substrate of 160-Kilodalton-dependent plasma membrane translocation but not Golgi-localized g-ear-containing Arf-binding protein-dependent entry into the insulin-responsive storage compartment.

Newly synthesized glucose transporter 4 (GLUT4) enters into the insulin-responsive storage compartment in a process that is Golgi-localized γ-ear-containing Arf-binding protein (GGA) dependent, whereas insulin-stimulated translocation is regulated by Akt substrate of 160 kDa (AS160). In the present study, using a variety of GLUT4/GLUT1 chimeras, we have analyzed the specific motifs of GLUT4 that are important for GGA and AS160 regulation of GLUT4 trafficking. Substitution of the amino terminus and the large intracellular loop of GLUT4 into GLUT1 (chimera 1-441) fully recapitulated the basal state retention, insulin-stimulated translocation, and GGA and AS160 sensitivity of wild-type GLUT4 (GLUT4-WT). GLUT4 point mutation (GLUT4-F5A) resulted in loss of GLUT4 intracellular retention in the basal state when coexpressed with both wild-type GGA and AS160. Nevertheless, similar to GLUT4-WT, the insulin-stimulated plasma membrane localization of GLUT4-F5A was significantly inhibited by coexpression of dominant-interfering GGA. In addition, coexpression with a dominant-interfering AS160 (AS160-4P) abolished insulin-stimulated GLUT4-WT but not GLUT4-F5A translocation. GLUT4 endocytosis and intracellular sequestration also required both the amino terminus and large cytoplasmic loop of GLUT4. Furthermore, both the FQQI and the SLL motifs participate in the initial endocytosis from the plasma membrane; however, once internalized, unlike the FQQI motif, the SLL motif is not responsible for intracellular recycling of GLUT4 back to the specialized compartment. Together, we have demonstrated that the FQQI motif within the amino terminus of GLUT4 is essential for GLUT4 endocytosis and AS160-dependent intracellular retention but not for the GGA-dependent sorting of GLUT4 into the insulin-responsive storage compartment.

Efeito do armazenamento na qualidade fisiológica das sementes de populações de milho cultivadas sob estresses hídrico e mineral

O objetivo deste trabalho foi avaliar o efeito do armazenamento na qualidade fisiológica de sementes de cinco populações de milho submetidas aos estresses de Al no solo e de seca no florescimento. Cinco populações de milho (CMS06, CMS35, CMS36, CMS54 e Milho Metro) foram cultivadas em solos com dois níveis de fertilidade: o primeiro, apresentando alta saturação de bases (V = 67%), e o segundo, alta saturação de Al (m = 54%). As populações de milho foram também submetidas à irrigação plena e à supressão de irrigação durante o florescimento. As sementes obtidas dessas populações foram armazenadas no laboratório de sementes sob condições ambientais. A qualidade fisiológica das sementes foi determinada no início e aos 30, 90 e 210 dias de armazenamento. As sementes da população CMS36 apresentaram maior vigor quando produzidas em solos com alta saturação de alumínio. A população CMS54 foi a mais estável com relação à qualidade fisiológica das sementes produzidas em diferentes ambientes. As sementes das populações CMS35, CMS36, CMS54 e Milho Metro foram mais estáveis com relação à qualidade fisiológica, durante o período de armazenamento, do que as da CMS06.

Administration of IL-18BP by gene therapy reduces inflammation and prevents joint destruction by downregulation of MMP-9 in rat AIA Role of MMP-9 in bone and joint destruction in arthritis

Background and objectives: Interleukin-18 (IL-18) is a pleiotropic cytokine involved in rheumatoid arthritis (RA) pathogenesis. This studywas carried out to evaluate the efficicacy of interleukin-18 binding protein (IL-18BP) gene therapy in the rat adjuvant-induced arthritis (AIA) model and to decipher the mechanisms by which IL-18BP delivery lessens bone destruction. Materials and methods: Arthritis was induced in female Lewis rat by Mycobacterium butyricum and the mRNA expression of IL-18 and IL-18BP was determined in the joints. In a preventative study, rats were divided into an adenovirus producing IL-18BP-Fc (AdmIL-18BP-Fc) group (n=8) and an adenovirus producing green fluorescent protein (AdGFP) group (n=7). On day 8 after AIA induction, adenoviruses were injected. Clinical parameters were assessed. At day 18, during maximal arthritis, the rats were euthanized, ankles were collected, and X-rays were performed. mRNA and protein were extracted from joints for analyses by qRT-PCR, multiplex, Western blot, and zymography. Results: We observed a decrease in the [IL-18BP/IL-18] ratio from day 7 to day 45. Administration of AdmIL-18BPd-Fc decreased clinical parameters and prevented bone and joint destruction compared to AdGFP administration. IL-18BP delivery reduced the metalloproteinase 9 (MMP-9) levels by 33% (at protein level (Fig. 1B) and functional level (Fig. 1C) and the tartrate-resistant acid phosphatase (TRAP) level by 44% (Fig. 1D) in the joint homogenates from AdmIL-18BPd-Fc compared to AdGFP treated rats.However, no variationwas observed forMMP-2 at the protein level (Fig.1A) and functional level (Fig. 1C). Conclusions: In rat AIA, a decrease in the [IL-18BP/ IL-18] ratio was observed. IL-18BP delivery prevented joint and bone destruction by downregulating MMP-9 and TRAP, suggesting a potential benefit of a similar therapy in RA.

Addition of stabilized wood ashes to Swedish coniferous stands on mineral soils : effects on stem growth and needle nutrient concentrations

Abstract

Essential residues in the H-NS binding site of Hha, a co-regulator of horizontally acquired genes in Enterobacteria

Proteins of the Hha/YmoA family co-regulate with H-NS the expression of horizontally acquired genes in Enterobacteria. Systematic mutations of conserved acidic residues in Hha have allowed the identification of D48 as an essential residue for H-NS binding and the involvement of E25. Mutations of these residues resulted in deregulation of sensitive genes in vivo. D48 is only partially solvent accessible, yet it defines the functional binding interface between Hha and H-NS confirming that Hha has to undergo a conformational change to bind H-NS. Exposed acidic residues, such as E25, may electrostatically facilitate and direct the approach of Hha to the positively charged region of H-NS enabling the formation of the final complex when D48 becomes accessible by a conformational change of Hha.

Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism

c-Src is a non-receptor tyrosine kinase involved in numerous signal transduction pathways. The kinase,SH3 and SH2 domains of c-Src are attached to the membrane-anchoring SH4 domain through the flexible Unique domain. Here we show intra- and intermolecular interactions involving the Unique and SH3 domains suggesting the presence of a previously unrecognized additional regulation layer in c-Src. We have characterized lipid binding by the Unique and SH3 domains, their intramolecular interaction and its allosteric modulation by a SH3-binding peptide or by Calcium-loaded calmodulin binding to the Unique domain. We also show reduced lipid binding following phosphorylation at conserved sites of the Unique domain. Finally, we show that injection of full-length c-Src with mutations that abolish lipid binding by the Unique domain causes a strong in vivo phenotype distinct from that of wild-type c-Src in a Xenopus oocyte model system, confirming the functional role of the Unique domain in c-Src regulation.

Nutrição mineral de mudas de pupunheira sob diferentes níveis de salinidade

O potencial produtivo das plantas pode ser afetado por desordens nutricionais, induzidas pelo estresse salino. O objetivo deste trabalho foi estudar a influência de diferentes níveis de salinidade na nutrição mineral de mudas de pupunheira (Bactris gasipaes H.B.K.), mediante o uso de solução nutritiva, em casa de vegetação. O experimento foi instalado em blocos ao acaso, com sete tratamentos e quatro repetições. Os tratamentos constaram das seguintes doses (mmol L-1): 0,0 de Na e 0,5 de Cl; 1,0 de Na e 0,5 de Cl (controle); e 5,0, 15,0, 30,0, 60,0 e 120,0 de NaCl. Os teores dos macronutrientes variaram em razão da salinidade, e verificou-se que o P e K apresentaram seus teores reduzidos nas raízes, o K e o Ca, nas folhas e o S, nas diferentes partes, enquanto o Na e o Cl apresentaram teores incrementados nas diferentes partes da planta. As relações Na/K, Na/Ca, Na/Mg, Cl/N, Cl/P e Cl/S aumentaram, causando um desbalanço nutricional na planta.

Influência de doses de calcário com diferentes relações cálcio: magnésio na produção de matéria seca e na composição mineral da alfafa

A acidez dos solos brasileiros, com alumínio em níveis tóxicos e baixa disponibilidade de elementos essenciais, principalmente o fósforo, exige aplicações de calcário e fertilizantes para a adequada utilização agrícola. Este trabalho objetivou avaliar o efeito de quatro doses de calcário calculadas com base no teor de Al3+ trocável do solo e em cinco relações molares de Ca:Mg, na produção de matéria seca e na composição mineral da alfafa. Duas cultivares de alfafa, Flórida 77 e Crioula, foram cultivadas em Latossolo Vermelho-Amarelo álico, textura argilosa, em casa de vegetação, em esquema fatorial disposto no delineamento inteiramente casualizado, com quatro repetições. A produção de matéria seca da parte aérea das duas cultivares aumentou em razão do aumento das doses de calcário, e somente a cultivar Flórida 77 apresentou diferenças significativas entre as relações molares Ca:Mg. Os teores de Ca, Mg e N na matéria seca da parte aérea, de modo geral, aumentaram em razão do aumento na quantidade de calcário, sendo somente os teores de Ca e Mg alterados pelas diferentes relações molares de Ca:Mg. Os teores de P e K, de modo geral, apresentaram pequenos decréscimos com a elevação das doses de calcário, embora considerados satisfatórios para a nutrição da alfafa.

ABS: a database of Annotated regulatory Binding Sites from orthologous promoters

Information about the genomic coordinates and the sequence of experimentally identified transcription factor binding sites is found scattered under a variety of diverse formats. The availability of standard collections of such high-quality data is important to design, evaluate and improve novel computational approaches to identify binding motifs on promoter sequences from related genes. ABS (http://genome.imim.es/datasets/abs2005/index.html) is a public database of known binding sites identified in promoters of orthologous vertebrate genes that have been manually curated from bibliography. We have annotated 650 experimental binding sites from 68 transcription factors and 100 orthologous target genes in human, mouse, rat or chicken genome sequences. Computational predictions and promoter alignment information are also provided for each entry. A simple and easy-to-use web interface facilitates data retrieval allowing different views of the information. In addition, the release 1.0 of ABS includes a customizable generator of artificial datasets based on the known sites contained in the collection and an evaluation tool to aid during the training and the assessment of motif-finding programs.

Adsorption of glyphosate in chilean soils and its relationship with unoccupied phosphate binding sites

The objective of this work was to investigate glyphosate adsorption by soils and its relationship with unoccupied binding sites for phosphate adsorption. Soil samples of three Chilean soils series - Valdivia (Andisol), Clarillo (Inceptisol) and Chicureo (Vertisol) - were incubated with different herbicide concentrations. Glyphosate remaining in solution was determined by adjusting a HPLC method with a UV detector. Experimental maximum adsorption capacity were 15,000, 14,300 and 4,700 mg g¹ for Valdivia, Clarillo, and Chicureo soils, respectively. Linear, Freundlich, and Langmuir models were used to describe glyphosate adsorption. Isotherms describing glyphosate adsorption differed among soils. Maximum adjusted adsorption capacity with the Langmuir model was 231,884, 17,874 and 5,670 mg g-1 for Valdivia, Clarillo, and Chicureo soils, respectively. Glyphosate adsorption on the Valdivia soil showed a linear behavior at the range of concentrations used and none of the adjusted models became asymptotic. The high glyphosate adsorption capacity of the Valdivia soil was probably a result of its high exchangeable Al, extractable Fe, and alophan and imogolite clay type. Adsorption was very much related to phosphate dynamics in the Valdivia soil, which showed the larger unoccupied phosphate binding sites. However relationship between unoccupied phosphate binding sites and glyphosate adsorption in the other two soils (Clarillo and Chicureo) was not clear.