bluuebunny/crossref_metadata_2025_split huggingface dataset:
From sequence to dynamics: the effects of transcription factor and polymerase concentration changes on activated and repressed promoters
Authors: González Pérez Abel , Espinosa Angarica Vladimir , Collado-Vides Julio , Vasconcelos Ana Tereza Ribeiro 
Published: September 2009

Abstract

Background
The fine tuning of two features of the bacterial regulatory machinery have been known to contribute to the diversity of gene expression within the same regulon: the sequence of Transcription Factor (TF) binding sites, and their location with respect to promoters. While variations of binding sequences modulate the strength of the interaction between the TF and its binding sites, the distance between binding sites and promoters alter the interaction between the TF and the RNA polymerase (RNAP).

Results
In this paper we estimated the dissociation constants (K

d
) of several E. coli TFs in their interaction with variants of their binding sequences from the scores resulting from aligning them to Positional Weight Matrices. A correlation coefficient of 0.78 was obtained when pooling together sites for different TFs. The theoretically estimated K

d
values were then used, together with the dissociation constants of the RNAP-promoter interaction to analyze activated and repressed promoters. The strength of repressor sites -- i.e., the strength of the interaction between TFs and their binding sites -- is slightly higher than that of activated sites. We explored how different factors such as the variation of binding sequences, the occurrence of more than one binding site, or different RNAP concentrations may influence the promoters' response to the variations of TF concentrations. We found that the occurrence of several regulatory sites bound by the same TF close to a promoter -- if they are bound by the TF in an independent manner -- changes the effect of TF concentrations on promoter occupancy, with respect to individual sites. We also found that the occupancy of a promoter will never be more than half if the RNAP concentration-to-K

p
ratio is 1 and the promoter is subject to repression; or less than half if the promoter is subject to activation. If the ratio falls to 0.1, the upper limit of occupancy probability for repressed drops below 10%; a descent of the limits occurs also for activated promoters.

Conclusion
The number of regulatory sites may thus act as a versatility-producing device, in addition to serving as a source of robustness of the transcription machinery. Furthermore, our results show that the effects of TF concentration fluctuations on promoter occupancy are constrained by RNAP concentrations.
Characterization of WRKYco-regulatory networks in rice and Arabidopsis
Authors: Berri Stefano , Abbruscato Pamela , Faivre-Rampant Odile , Brasileiro Ana CM , Fumasoni Irene , Satoh Kouji , Kikuchi Shoshi , Mizzi Luca , Morandini Piero , Pè Mario Enrico , Piffanelli Pietro 
Published: September 2009

AbstractBackgroundThe WRKY transcription factor gene family has a very ancient origin and has undergone extensive duplications in the plant kingdom. Several studies have pointed out their involvement in a range of biological processes, revealing that a large number ofWRKYgenes are transcriptionally regulated under conditions of biotic and/or abiotic stress. To investigate the existence ofWRKYco-regulatory networks in plants, a whole gene familyWRKYs expression study was carried out in rice (Oryza sativa). This analysis was extended toArabidopsis thalianataking advantage of an extensive repository of gene expression data.ResultsThe presented results suggested that 24 members of the riceWRKYgene family (22% of the total) were differentially-regulated in response to at least one of the stress conditions tested. We defined the existence of nine OsWRKYgene clusters comprising both phylogenetically related and unrelated genes that were significantly co-expressed, suggesting that specific sets ofWRKYgenes might act in co-regulatory networks. This hypothesis was tested by Pearson Correlation Coefficient analysis of the ArabidopsisWRKYgene family in a large set of Affymetrix microarray experiments.AtWRKYswere found to belong to two main co-regulatory networks (COR-A, COR-B) and two smaller ones (COR-C and COR-D), all including genes belonging to distinct phylogenetic groups. The COR-A network contained severalAtWRKYgenes known to be involved mostly in response to pathogens, whose physical and/or genetic interaction was experimentally proven. We also showed that specific co-regulatory networks were conserved between the two model species by identifying Arabidopsis orthologs of the co-expressedOsWRKYgenes.ConclusionIn this work we identified sets of co-expressedWRKYgenes in both rice and Arabidopsis that are functionally likely to cooperate in the same signal transduction pathways. We propose that, making use of data from co-regulatory networks, it is possible to highlight novel clusters of plant genes contributing to the same biological processes or signal transduction pathways. Our approach will contribute to unveil gene cooperation pathways not yet identified by classical genetic analyses. This information will open new routes contributing to the dissection of WRKY signal transduction pathways in plants.
Inversion 2La is associated with enhanced desiccation resistance in Anopheles gambiae
Authors: Gray Emilie M , Rocca Kyle AC , Costantini Carlo , Besansky Nora J 
Published: September 2009

Abstract

Background

Anopheles gambiae, the principal vector of malignant malaria in Africa, occupies a wide range of habitats. Environmental flexibility may be conferred by a number of chromosomal inversions non-randomly associated with aridity, including 2La. The purpose of this study was to determine the physiological mechanisms associated with the 2La inversion that may result in the preferential survival of its carriers in hygrically-stressful environments.

Methods
Two homokaryotypic populations of A. gambiae (inverted 2La and standard 2L+a) were created from a parental laboratory colony polymorphic for 2La and standard for all other known inversions. Desiccation resistance, water, energy and dry mass of adult females of both populations were compared at several ages and following acclimation to a more arid environment.

Results
Females carrying 2La were significantly more resistant to desiccation than 2L+a females at emergence and four days post-emergence, for different reasons. Teneral 2La females had lower rates of water loss than their 2L+a counterparts, while at four days, 2La females had higher initial water content. No differences in desiccation resistance were found at eight days, with or without acclimation. However, acclimation resulted in both populations significantly reducing their rates of water loss and increasing their desiccation resistance. Acclimation had contrasting effects on the body characteristics of the two populations: 2La females boosted their glycogen stores and decreased lipids, whereas 2La females did the contrary.

Conclusion
Variation in rates of water loss and response to acclimation are associated with alternative arrangements of the 2La inversion. Understanding the mechanisms underlying these traits will help explain how inversion polymorphisms permit exploitation of a heterogeneous environment by this disease vector.
Genes encoding novel secreted and transmembrane proteins are temporally and spatially regulated during Drosophila melanogasterembryogenesis
Authors: Zúñiga Alejandro , Hödar Christian , Hanna Patricia , Ibáñez Freddy , Moreno Pablo , Pulgar Rodrigo , Pastenes Luis , González Mauricio , Cambiazo Verónica 
Published: September 2009

Abstract

Background

Morphogenetic events that shape the Drosophila melanogaster embryo are tightly controlled by a genetic program in which specific sets of genes are up-regulated. We used a suppressive subtractive hybridization procedure to identify a group of developmentally regulated genes during early stages of D. melanogaster embryogenesis. We studied the spatiotemporal activity of these genes in five different intervals covering 12 stages of embryogenesis.

Results

Microarrays were constructed to confirm induction of expression and to determine the temporal profile of isolated subtracted cDNAs during embryo development. We identified a set of 118 genes whose expression levels increased significantly in at least one developmental interval compared with a reference interval. Of these genes, 53% had a phenotype and/or molecular function reported in the literature, whereas 47% were essentially uncharacterized. Clustering analysis revealed demarcated transcript groups with maximum gene activity at distinct developmental intervals. In situ hybridization assays were carried out on 23 uncharacterized genes, 15 of which proved to have spatiotemporally restricted expression patterns. Among these 15 uncharacterized genes, 13 were found to encode putative secreted and transmembrane proteins. For three of them we validated our protein sequence predictions by expressing their cDNAs in Drosophila S2R+ cells and analyzed the subcellular distribution of recombinant proteins. We then focused on the functional characterization of the gene CG6234. Inhibition of CG6234 by RNA interference resulted in morphological defects in embryos, suggesting the involvement of this gene in germ band retraction.

Conclusion

Our data have yielded a list of developmentally regulated D. melanogaster genes and their expression profiles during embryogenesis and provide new information on the spatiotemporal expression patterns of several uncharacterized genes. In particular, we recovered a substantial number of unknown genes encoding putative secreted and transmembrane proteins, suggesting new components of signaling pathways that might be incorporated within the existing regulatory networks controlling D. melanogaster embryogenesis. These genes are also good candidates for additional targeted functional analyses similar to those we conducted for CG6234.
See related minireview by Vichas and Zallen: http://www.jbiol.com/content/8/8/76
Effect of nutritional recovery with soybean flour diet on body composition, energy balance and serum leptin concentration in adult rats
Authors: Cheim Loanda Maria G , Oliveira Elisângela A , Arantes Vanessa C , Veloso Roberto V , Reis Marise Auxiliadora B , Gomes-da-Silva Maria Helena G , Carneiro Everardo M , Boschero Antonio C , Latorraca Márcia Q 
Published: September 2009

AbstractBackgroundMalnutrition in early life is associated with obesity in adulthood and soybean products may have a beneficial effect on its prevention and treatment. This study evaluated body composition, serum leptin and energy balance in adult rats subjected to protein restriction during the intrauterine stage and lactation and recovering on a soybean flour diet.MethodsFive groups of the Wistar strain of albino rats were used: CC, offspring born to and suckled by mothers fed a control diet and fed the same diet after weaning; CS, offspring born to and suckled by mothers fed a control diet and fed a soybean diet with 17% protein after weaning; LL, offspring of mothers fed a low protein diet and fed the same diet after weaning; LC, offspring of mothers fed a low protein diet, but fed a control diet after weaning; LS, offspring of mothers fed a low protein diet, but fed a soybean diet with 17% protein after weaning. Food intake, body, perirenal and retroperitoneal adipose tissue were measured in grams. Leptin was quantified using the Enzyme Linked Immuno Sorbent Assay (ELISA) and insulin by radioimmunoassay (RIA). Carcass composition was determined by chemical methods and energy expenditure was calculated by the difference between energy intake and carcass energy gain. Data were tested by analysis of variance (ANOVA).ResultsThe LC and LS groups had higher energetic intake concerning body weight, lower energy expenditure, proportion of fat carcass and fat pads than CC and CS groups. The LS group showed reduced body weight gain and lower energy efficiency, which was reflected in less energy gain as protein and the proportion of carcass protein, and lower energy gain as lipid than in the LC groups, although both groups had eaten the same amount of diet and showed equal energy expenditure. Serum leptin did not differ among groups and was unrelated to food or energy intake and energy expenditure. Serum insulin was higher in the LS than in the LC group.ConclusionProtein restriction during intrauterine life and lactation periods did not provoke obesity in adulthood. Nutritional recovery with soybean diet decreased the body weight at the expense of lower energy efficiency with repercussion on lean mass.
An overview of cardiovascular risk factor burden in sub-Saharan African countries: a socio-cultural perspective
Authors: BeLue Rhonda , Okoror Titilayo A , Iwelunmor Juliet , Taylor Kelly D , Degboe Arnold N , Agyemang Charles , Ogedegbe Gbenga 
Published: September 2009

Abstract

Background
Sub-Saharan African (SSA) countries are currently experiencing one of the most rapid epidemiological transitions characterized by increasing urbanization and changing lifestyle factors. This has resulted in an increase in the incidence of non-communicable diseases, especially cardiovascular disease (CVD). This double burden of communicable and chronic non-communicable diseases has long-term public health impact as it undermines healthcare systems.

Purpose
The purpose of this paper is to explore the socio-cultural context of CVD risk prevention and treatment in sub-Saharan Africa. We discuss risk factors specific to the SSA context, including poverty, urbanization, developing healthcare systems, traditional healing, lifestyle and socio-cultural factors.

Methodology
We conducted a search on African Journals On-Line, Medline, PubMed, and PsycINFO databases using combinations of the key country/geographic terms, disease and risk factor specific terms such as "diabetes and Congo" and "hypertension and Nigeria". Research articles on clinical trials were excluded from this overview. Contrarily, articles that reported prevalence and incidence data on CVD risk and/or articles that report on CVD risk-related beliefs and behaviors were included. Both qualitative and quantitative articles were included.

Results
The epidemic of CVD in SSA is driven by multiple factors working collectively. Lifestyle factors such as diet, exercise and smoking contribute to the increasing rates of CVD in SSA. Some lifestyle factors are considered gendered in that some are salient for women and others for men. For instance, obesity is a predominant risk factor for women compared to men, but smoking still remains mostly a risk factor for men. Additionally, structural and system level issues such as lack of infrastructure for healthcare, urbanization, poverty and lack of government programs also drive this epidemic and hampers proper prevention, surveillance and treatment efforts.

Conclusion
Using an African-centered cultural framework, the PEN3 model, we explore future directions and efforts to address the epidemic of CVD risk in SSA.
Modeling system states in liver cells: Survival, apoptosis and their modifications in response to viral infection
Authors: Philippi Nicole , Walter Dorothee , Schlatter Rebekka , Ferreira Karine , Ederer Michael , Sawodny Oliver , Timmer Jens , Borner Christoph , Dandekar Thomas 
Published: September 2009

Abstract

Background
The decision pro- or contra apoptosis is complex, involves a number of different inputs, and is central for the homeostasis of an individual cell as well as for the maintenance and regeneration of the complete organism.

Results
This study centers on Fas ligand (FasL)-mediated apoptosis, and a complex and internally strongly linked network is assembled around the central FasL-mediated apoptosis cascade. Different bioinformatical techniques are employed and different crosstalk possibilities including the integrin pathway are considered. This network is translated into a Boolean network (74 nodes, 108 edges). System stability is dynamically sampled and investigated using the software SQUAD. Testing a number of alternative crosstalk possibilities and networks we find that there are four stable system states, two states comprising cell survival and two states describing apoptosis by the intrinsic and the extrinsic pathways, respectively. The model is validated by comparing it to experimental data from kinetics of cytochrome c release and caspase activation in wildtype and Bid knockout cells grown on different substrates. Pathophysiological modifications such as input from cytomegalovirus proteins M36 and M45 again produces output behavior that well agrees with experimental data.

Conclusion
A network model for apoptosis and crosstalk in hepatocytes shows four different system states and reproduces a number of different conditions around apoptosis including effects of different growth substrates and viral infections. It produces semi-quantitative predictions on the activity of individual nodes, agreeing with experimental data. The model (SBML format) and all data are available for further predictions and development.
Multicenter Randomized Phase II Study of Weekly or Twice-Weekly Bortezomib Plus Rituximab in Patients With Relapsed or Refractory Follicular or Marginal-Zone B-Cell Lymphoma
Authors: de Vos Sven , Goy André , Dakhil Shaker R. , Saleh Mansoor N. , McLaughlin Peter , Belt Robert , Flowers Christopher R. , Knapp Mark , Hart Lowell , Patel-Donnelly Dipti , Glenn Martha , Gregory Stephanie A. , Holladay Charles , Zhang Tracy , Boral Anthony L. 
Published: September 2009

Purpose To determine overall response rate (ORR), time to progression (TTP), and duration of response (DOR) with twice-weekly/weekly bortezomib plus rituximab, and evaluate safety/tolerability, in patients with relapsed or refractory CD20+ follicular lymphoma (FL) or marginal-zone lymphoma. Patients and Methods Patients were randomly assigned (minimization method) to bortezomib 1.3 mg/m2 twice weekly (days 1, 4, 8, and 11; 21-day cycle, five cycles; arm A) or bortezomib 1.6 mg/m2 weekly (days 1, 8, 15, and 22; 35-day cycle, three cycles; arm B) plus rituximab 375 mg/m2 weekly for 4 weeks (both arms). Response/progression was determined by International Workshop Response Criteria using oncologist/radiologist-adjudicated data from independent radiology review and investigator assessment. Results Eighty-one patients (arm A, n = 41; arm B, n = 40) were enrolled. Dose-intensity was higher in arm A; mean total bortezomib received was similar between arms (18.5 and 17.1 mg/m2). In arm A, ORR was 49% (14% complete response [CR]/CR unconfirmed [CRu]), median TTP was 7.0 months, and median DOR was not reached. In arm B, ORR was 43% (10% CR/CRu), and median TTP/DOR were 10.0/9.3 months. The weekly combination regimen seemed better tolerated. Grade 3 or worse adverse events seemed more common in arm A (54%) versus arm B (35%), including thrombocytopenia (10% v 0%) and peripheral neuropathy (10% v 5%), but diarrhea seemed less frequent (7% v 15%). No grade 4 toxicities were reported in arm B. Conclusion Both bortezomib plus rituximab regimens seem feasible in relapsed or refractory indolent lymphomas. The more convenient weekly combination regimen is being compared with single-agent rituximab in an ongoing phase III study in relapsed FL.
Pegylated Liposomal Doxorubicin Plus Docetaxel Significantly Improves Time to Progression Without Additive Cardiotoxicity Compared With Docetaxel Monotherapy in Patients With Advanced Breast Cancer Previously Treated With Neoadjuvant-Adjuvant Anthracycline Therapy: Results From a Randomized Phase III Study
Authors: Sparano Joseph A. , Makhson Anatoly N. , Semiglazov Vladimir F. , Tjulandin Sergei A. , Balashova Olga I. , Bondarenko Igor N. , Bogdanova Natalia V. , Manikhas George M. , Oliynychenko Gennadiy P. , Chatikhine Valery A. , Zhuang Sen H. , Xiu Liang , Yuan Zhilong , Rackoff Wayne R. 
Published: September 2009

Purpose To determine whether the combination of pegylated liposomal doxorubicin (PLD) and docetaxel significantly prolongs time to disease progression compared with docetaxel alone without an increase in cardiac toxicity in women with advanced breast cancer who had experienced relapse at least 1 year after prior adjuvant or neoadjuvant anthracycline therapy. Patients and Methods This international, phase III study randomly assigned 751 patients to receive either docetaxel 75 mg/m2 (n = 373) or PLD 30 mg/m2 followed by docetaxel 60 mg/m2 every 21 days (n = 378) and continued until disease progression or prohibitive toxicity. The primary end point was time to progression (TTP). Secondary end points were overall survival (OS), objective response rate (ORR), cardiac toxicity, and safety. Results Treatment with PLD-docetaxel significantly improved median TTP from 7.0 to 9.8 months (hazard ratio [HR] = 0.65; 95% CI, 0.55 to 0.77; P = .000001) and the ORR from 26% to 35% (P = .0085). OS was similar between the two groups (HR = 1.02; 95% CI, 0.86 to 1.22). The incidence of grade 3 or 4 adverse events were similar (78% v 72%), although a higher incidence of hand-foot syndrome (24% v 0%) and mucositis/stomatitis (12% v 1%) were observed in the PLD-docetaxel combination. Protocol-defined left ventricular ejection fraction decreases and congestive heart failure were reported in 5% and 1% in both treatment arms, respectively. Conclusion The PLD-docetaxel combination was more effective than docetaxel alone in women with metastatic breast cancer who had experienced relapse at least 1 year after prior adjuvant anthracycline therapy without an increase in cardiac toxicity, although mucocutaneous toxicity was more common.
Prognostic Significance of Copy-Number Alterations in Multiple Myeloma
Authors: Avet-Loiseau Hervé , Li Cheng , Magrangeas Florence , Gouraud Wilfried , Charbonnel Catherine , Harousseau Jean-Luc , Attal Michel , Marit Gerald , Mathiot Claire , Facon Thierry , Moreau Philippe , Anderson Kenneth C. , Campion Loïc , Munshi Nikhil C. , Minvielle Stéphane 
Published: September 2009

Purpose Chromosomal aberrations are a hallmark of multiple myeloma but their global prognostic impact is largely unknown. Patients and Methods We performed a genome-wide analysis of malignant plasma cells from 192 newly diagnosed patients with myeloma using high-density, single-nucleotide polymorphism (SNP) arrays to identify genetic lesions associated with prognosis. Results Our analyses revealed deletions and amplifications in 98% of patients. Amplifications in 1q and deletions in 1p, 12p, 14q, 16q, and 22q were the most frequent lesions associated with adverse prognosis, whereas recurrent amplifications of chromosomes 5, 9, 11, 15, and 19 conferred a favorable prognosis. Multivariate analysis retained three independent lesions: amp(1q23.3), amp(5q31.3), and del(12p13.31). When adjusted to the established prognostic variables (ie, t(4;14), del(17p), and serum β2-microglobulin [Sβ2M]), del(12p13.31) remained the most powerful independent adverse marker (P < .0001; hazard ratio [HR], 3.17) followed by Sβ2M (P < .0001; HR, 2.78) and the favorable marker amp(5q31.3) (P = .0005; HR, 0.37). Patients with amp(5q31.3) alone and low Sβ2M had an excellent prognosis (5-year overall survival, 87%); conversely, patients with del(12p13.31) alone or amp(5q31.3) and del(12p13.31) and high Sβ2M had a very poor outcome (5-year overall survival, 20%). This prognostic model was validated in an independent validation cohort of 273 patients with myeloma. Conclusion These findings demonstrate the power and accessibility of molecular karyotyping to predict outcome in myeloma. In addition, integration of expression of genes residing in the lesions of interest revealed putative features of the disease driving short survival.