Alteration of glucose metabolism in cultured astrocytes after AQP9-small interference RNA application.

Aquaglyceroporin-9 (AQP9) facilitates diffusion of water and energy substrates such as glycerol and monocarboxylates. AQP9 is present in plasma membrane and mitochondria of astrocytes and catecholaminergic neurons, suggesting that it plays a role in the energetic status of these cells. Using specific small interference RNA directed against AQP9 in astrocyte cultures, we showed that glycerol uptake is decreased which is associated with an increase in glucose uptake and oxidative metabolism. Our results not only confirm the presence of AQP9 in astrocytes but also suggest that changes in AQP9 expression alter glial energy metabolism.

Predicted effects of small decreases in energy expenditure on weight gain in adult women.

Small daily positive energy imbalances of 200 to 800 kJ (about 50 to 200 kcal) due to reduced resting energy expenditure (REE), reduced diet-induced thermogenesis, or physical inactivity are believed to predispose to obesity. However, estimates of the magnitude of the weight gain often fail to account for concurrent changes in body composition and increases in maintenance energy requirements as weight increases and energy equilibrium is re-established. Using previously reported data on body composition and REE in women and the energy cost of tissue deposition, we used mathematical models to predict the theoretical effect of a persistent reduction in energy expenditure on long-term weight gain, assuming no adaptation in energy intake. The analyses indicate the following effects of a reduced level of energy expenditure in lean and obese women: (i) REE rises more slowly with increasing degrees of obesity due to a declining proportion of the more metabolically active fat-free mass; so, for the same positive energy balance, a significantly greater weight gain is expected for obese than for lean women before energy equilibrium is re-established; (ii) due to the greater energy density of adipose tissue, the time course of weight gain to achieve energy balance is longer for obese subjects: in general, this is approximately five years for lean and ten years for obese women; (iii) the magnitude of weight gain of lean women in response to a reduced energy expenditure of 200 to 800 kJ/day is only about 3 to 15 kg, amounts insufficient to explain severe obesity.

LSTA Five Year Plan, 1998-2002, 2002

The LSTA goals for Iowa, FY98-FY02, are as follows: 1. Provide all Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network. 2. Improve library service to Iowans through knowledgeable, well-trained staff and wellinformed public library trustees and library users. 3. Meet Iowans’ increasing demands for information and library services by identifying and encouraging resource sharing and partnerships. 4. Provide state level leadership and services to accomplish the LSTA Five-Year Plan. The primary objectives of this evaluation are to provide: $ An assessment of the overall impact of Iowa’s LSTA funding and success in achieving the goals identified in the state’s five-year plan. $ An in-depth analysis of two specific goals from the plan: providing Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network; and improving library service to Iowans through knowledgeable, well-trained staff and well-informed public library trustees and library users. LSTA built on accomplishments made possible with the federal HEA II-B grant awarded to the State Library in 1995. This grant led the way in bringing technology to Iowa libraries by creating an electronic library network for resource sharing. SILO (State of Iowa Libraries Online) became fully functional in 1997. The State Library continued funding SILO with LSTA money when the grant ended. This funding supports the SILO infrastructure, providing equitable access to information through cutting edge technology to Iowans in both small and large, rural and urban, communities. Access to electronic material and information has encouraged public libraries to increase the number of computers and public access to the Internet. LSTA funding was used to increase training opportunities for library staff and trustees. Many programs, such as librarian certification, were strengthened by an increase in continuing education opportunities.

LSTA Five Year Plan, 1998-2002, 2002

The LSTA goals for Iowa, FY98-FY02, are as follows: 1. Provide all Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network. 2. Improve library service to Iowans through knowledgeable, well-trained staff and wellinformed public library trustees and library users. 3. Meet Iowans’ increasing demands for information and library services by identifying and encouraging resource sharing and partnerships. 4. Provide state level leadership and services to accomplish the LSTA Five-Year Plan. The primary objectives of this evaluation are to provide: $ An assessment of the overall impact of Iowa’s LSTA funding and success in achieving the goals identified in the state’s five-year plan. $ An in-depth analysis of two specific goals from the plan: providing Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network; and improving library service to Iowans through knowledgeable, well-trained staff and well-informed public library trustees and library users. LSTA built on accomplishments made possible with the federal HEA II-B grant awarded to the State Library in 1995. This grant led the way in bringing technology to Iowa libraries by creating an electronic library network for resource sharing. SILO (State of Iowa Libraries Online) became fully functional in 1997. The State Library continued funding SILO with LSTA money when the grant ended. This funding supports the SILO infrastructure, providing equitable access to information through cutting edge technology to Iowans in both small and large, rural and urban, communities. Access to electronic material and information has encouraged public libraries to increase the number of computers and public access to the Internet. LSTA funding was used to increase training opportunities for library staff and trustees. Many programs, such as librarian certification, were strengthened by an increase in continuing education opportunities.

LSTA Five Year Plan Evaluation, 1998-2002, 2002

The LSTA goals for Iowa, FY98-FY02, are as follows: 1. Provide all Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network. 2. Improve library service to Iowans through knowledgeable, well-trained staff and wellinformed public library trustees and library users. 3. Meet Iowans’ increasing demands for information and library services by identifying and encouraging resource sharing and partnerships. 4. Provide state level leadership and services to accomplish the LSTA Five-Year Plan. The primary objectives of this evaluation are to provide: $ An assessment of the overall impact of Iowa’s LSTA funding and success in achieving the goals identified in the state’s five-year plan. $ An in-depth analysis of two specific goals from the plan: providing Iowans with expanded access to information and materials through the State of Iowa Libraries Online (SILO) network; and improving library service to Iowans through knowledgeable, well-trained staff and well-informed public library trustees and library users. LSTA built on accomplishments made possible with the federal HEA II-B grant awarded to the State Library in 1995. This grant led the way in bringing technology to Iowa libraries by creating an electronic library network for resource sharing. SILO (State of Iowa Libraries Online) became fully functional in 1997. The State Library continued funding SILO with LSTA money when the grant ended. This funding supports the SILO infrastructure, providing equitable access to information through cutting edge technology to Iowans in both small and large, rural and urban, communities. Access to electronic material and information has encouraged public libraries to increase the number of computers and public access to the Internet. LSTA funding was used to increase training opportunities for library staff and trustees. Many programs, such as librarian certification, were strengthened by an increase in continuing education opportunities.

High-dose sequential chemotherapy (ICE) under circulating progenitor cells (CPC) protection in patients with small cell lung carcinoma (SCLC). Preliminary report on a multicentric study

Starting in February 1994, 20 patients (pt) with a median age of 50 years(range 41-63) from 7 European centers have been included. Completedata were obtained in 16 patients so far. CPC were mobilized with chemo(Epirubicine 75 mg/m2 /d, 01 + 02) followed by G-CSF 5 p.gfkg/d for14 days. HD chemo consisted in 3 sequential courses of ICE regimen(UOs. 10 g/m2 , Carbo. 1200 mg/m2 and Etop. 1200 mg/m2 ) underCPC protection and G-CSF 5 p.g/kg/d. Out of the 16 pt, 12 completedfull program (3 cycles). One pt died of septic shock before receivingany ICE course. One pt died during the first ICE of renal insufficiency.Two pt had only 2 courses because of toxicity. Among the 16 pt, responserate (RR) was: 7 CR, 6 PR, 1 PO; 3 pt are not evaluable dueto early withdrawal (overall RR: 13/16 = 81 %). Thirty-nine cycles ofHD chemo were given with a median hematological recovery of 9 days(range 7-12) until neutro. counts> 1.0 x 109 /1 and 9 days (range 717)until thrombo. > 20 x 109 /1. No cumulative, hematological toxicitywas seen. Accrual of patients is still ongoing and updated results will bepresented.

Purification and ligand binding of a soluble class I major histocompatibility complex molecule consisting of the first three domains of H-2Kd fused to beta 2-microglobulin expressed in the baculovirus-insect cell system.

A recombinant baculovirus encoding a single-chain murine major histocompatibility complex class I molecule in which the first three domains of H-2Kd are fused to beta 2-microglobulin (beta 2-m) via a 15-amino acid linker has been isolated and used to infect lepidopteran cells. A soluble, 391-amino acid single-chain H-2Kd (SC-Kd) molecule of 48 kDa was synthesized and glycosylated in insect cells and could be purified in the absence of detergents by affinity chromatography using the anti-H-2Kd monoclonal antibody SF1.1.1.1. We tested the ability of SC-Kd to bind antigenic peptides using a direct binding assay based on photoaffinity labeling. The photoreactive derivative was prepared from the H-2Kd-restricted Plasmodium berghei circumsporozoite protein (P.b. CS) peptide 253-260 (YIPSAEKI), a probe that we had previously shown to be unable to bind to the H-2Kd heavy chain in infected cells in the absence of co-expressed beta 2-microglobulin. SC-Kd expressed in insect cells did not require additional mouse beta 2-m to bind the photoprobe, indicating that the covalently attached beta 2-m could substitute for the free molecule. Similarly, binding of the P.b. CS photoaffinity probe to the purified SC-Kd molecule was unaffected by the addition of exogenous beta 2-m. This is in contrast to H-2KdQ10, a soluble H-2Kd molecule in which beta 2-m is noncovalently bound to the soluble heavy chain, whose ability to bind the photoaffinity probe is greatly enhanced in the presence of an excess of exogenous beta 2-m. The binding of the probe to SC-Kd was allele-specific, since labeling was selectively inhibited only by antigenic peptides known to be presented by the H-2Kd molecule.

GacA-controlled activation of promoters for small RNA genes in Pseudomonas fluorescens.

The Gac/Rsm signal transduction pathway positively regulates secondary metabolism, production of extracellular enzymes, and biocontrol properties of Pseudomonas fluorescens CHA0 via the expression of three noncoding small RNAs, termed RsmX, RsmY, and RsmZ. The architecture and function of the rsmY and rsmZ promoters were studied in vivo. A conserved palindromic upstream activating sequence (UAS) was found to be necessary but not sufficient for rsmY and rsmZ expression and for activation by the response regulator GacA. A poorly conserved linker region located between the UAS and the -10 promoter sequence was also essential for GacA-dependent rsmY and rsmZ expression, suggesting a need for auxiliary transcription factors. One such factor involved in the activation of the rsmZ promoter was identified as the PsrA protein, previously recognized as an activator of the rpoS gene and a repressor of fatty acid degradation. Furthermore, the integration host factor (IHF) protein was found to bind with high affinity to the rsmZ promoter region in vitro, suggesting that DNA bending contributes to the regulated expression of rsmZ. In an rsmXYZ triple mutant, the expression of rsmY and rsmZ was elevated above that found in the wild type. This negative feedback loop appears to involve the translational regulators RsmA and RsmE, whose activity is antagonized by RsmXYZ, and several hypothetical DNA-binding proteins. This highly complex network controls the expression of the three small RNAs in response to cell physiology and cell population densities.

Small RNAs in bacterialcell-cell communication

When all three separate quorum-sensing signals act in concert in Vibrio harveyi, they maximize bioluminescence and fully repress type III secretion. V. harveyi has five qrr loci encoding small RNA regulatory molecules, each consisting of about 100 nucleotides; several of them are involved in repressing bioluminescence. Small RNAs also play roles in population density-dependent activities, including regulation of virulence factors, for bacterial pathogens such as Pseudomonas fluorescens, V. cholerae, Salmonella enterica, Pseudomonas aeruginosa, and Erwinia spp. Although some bacteria appear to carry redundant copies of small RNA genes with which to finely tune expression

Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The Second ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on management of patients with non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, early stage disease, locally advanced disease and advanced (metastatic) disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on recommendations for pathology and molecular biomarkers in relation to the diagnosis of lung cancer, primarily non-small-cell carcinomas.

Asymmetric effects of monetary policy in the US: Positive vs. negative or big vs. small?

This paper reconsiders the empirical evidence on the asymmetricoutput effects of monetary policy. Asymmetric effects is a common feature ofmany theoretical models, and there are many different versions of suchasymmetries. We concentrate on the distinctions between positive andnegative money-supply changes, big and small changes in money-supply, andpossible combinations of the two asymmetries. Earlier research has foundempirical evidence in favor of the former of these in US data. Using M1 asthe monetary variable we find evidence in favor of neutrality of big shocksand non-neutrality of small shocks. The results may, however, be affected bystructual instability of M1 demand. Thus, we substitute M1 with the federalfunds rate. In these data we find that only small negative shocks affectreal aggregate activity. The results are interpreted in terms of menu-costmodels.

HTPSELEX--a database of high-throughput SELEX libraries for transcription factor binding sites.

HTPSELEX is a public database providing access to primary and derived data from high-throughput SELEX experiments aimed at characterizing the binding specificity of transcription factors. The resource is primarily intended to serve computational biologists interested in building models of transcription factor binding sites from large sets of binding sequences. The guiding principle is to make available all information that is relevant for this purpose. For each experiment, we try to provide accurate information about the protein material used, details of the wet lab protocol, an archive of sequencing trace files, assembled clone sequences (concatemers) and complete sets of in vitro selected protein-binding tags. In addition, we offer in-house derived binding sites models. HTPSELEX also offers reasonably large SELEX libraries obtained with conventional low-throughput protocols. The FTP site contains the trace archives and database flatfiles. The web server offers user-friendly interfaces for viewing individual entries and quality-controlled download of SELEX sequence libraries according to a user-defined sequencing quality threshold. HTPSELEX is available from ftp://ftp.isrec.isb-sib.ch/pub/databases/htpselex/ and http://www.isrec.isb-sib.ch/htpselex.