bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxic transcription gene profiles under the modulation of nitric oxide in nuclear run on-microarray and proteomics
Authors: Igwe Emeka I , Essler Silke , Al-Furoukh Natalie , Dehne Nathalie , Brüne Bernhard 
Published: September 2009

Abstract

Background
Microarray analysis still is a powerful tool to identify new components of the transcriptosome. It helps to increase the knowledge of targets triggered by stress conditions such as hypoxia and nitric oxide. However, analysis of transcriptional regulatory events remain elusive due to the contribution of altered mRNA stability to gene expression patterns as well as changes in the half-life of mRNAs, which influence mRNA expression levels and their turn over rates. To circumvent these problems, we have focused on the analysis of newly transcribed (nascent) mRNAs by nuclear run on (NRO), followed by microarray analysis.

Results
We identified 196 genes that were significantly regulated by hypoxia, 85 genes affected by nitric oxide and 292 genes induced by the cotreatment of macrophages with both NO and hypoxia. Fourteen genes (Bnip3, Ddit4, Vegfa, Trib3, Atf3, Cdkn1a, Scd1, D4Ertd765e, Sesn2, Son, Nnt, Lst1, Hps6 and Fxyd5) were common to all treatments but with different levels of expression in each group. We observed that 162 transcripts were regulated only when cells were co-treated with hypoxia and NO but not with either treatment alone, pointing to the importance of a crosstalk between hypoxia and NO. In addition, both array and proteomics data supported a consistent repression of hypoxia-regulated targets by NO.

Conclusion
By eliminating the interference of steady state mRNA in gene expression profiling, we obtained a smaller number of significantly regulated transcripts in our study compared to published microarray data and identified previously unknown hypoxia-induced targets. Gene analysis profiling corroborated the interplay between NO- and hypoxia-induced signaling.
A modified TILLING approach to detect induced mutations in tetraploid and hexaploid wheat
Authors: Uauy Cristobal , Paraiso Francine , Colasuonno Pasqualina , Tran Robert K , Tsai Helen , Berardi Steve , Comai Luca , Dubcovsky Jorge 
Published: September 2009

AbstractBackgroundWheat (Triticumssp.) is an important food source for humans in many regions around the world. However, the ability to understand and modify gene function for crop improvement is hindered by the lack of available genomic resources. TILLING is a powerful reverse genetics approach that combines chemical mutagenesis with a high-throughput screen for mutations. Wheat is specially well-suited for TILLING due to the high mutation densities tolerated by polyploids, which allow for very efficient screens. Despite this, few TILLING populations are currently available. In addition, current TILLING screening protocols require high-throughput genotyping platforms, limiting their use.ResultsWe developed mutant populations of pasta and common wheat and organized them for TILLING. To simplify and decrease costs, we developed a non-denaturing polyacrylamide gel set-up that uses ethidium bromide to detect fragments generated by crude celery juice extract digestion of heteroduplexes. This detection method had similar sensitivity as traditional LI-COR screens, suggesting that it represents a valid alternative. We developed genome-specific primers to circumvent the presence of multiple homoeologous copies of our target genes. Each mutant library was characterized by TILLING multiple genes, revealing high mutation densities in both the hexaploid (~1/38 kb) and tetraploid (~1/51 kb) populations for 50% GC targets. These mutation frequencies predict that screening 1,536 lines for an effective target region of 1.3 kb with 50% GC content will result in ~52 hexaploid and ~39 tetraploid mutant alleles. This implies a high probability of obtaining knock-out alleles (P= 0.91 for hexaploid,P= 0.84 for tetraploid), in addition to multiple missense mutations. In total, we identified over 275 novel alleles in eleven targeted gene/genome combinations in hexaploid and tetraploid wheat and have validated the presence of a subset of them in our seed stock.ConclusionWe have generated reverse genetics TILLING resources for pasta and bread wheat and achieved a high mutation density in both populations. We also developed a modified screening method that will lower barriers to adopt this promising technology. We hope that the use of this reverse genetics resource will enable more researchers to pursue wheat functional genomics and provide novel allelic diversity for wheat improvement.
Low-resolution structural studies of human Stanniocalcin-1
Authors: Trindade Daniel M , Silva Júlio C , Navarro Margareth S , Torriani Iris CL , Kobarg Jörg 
Published: September 2009

Abstract

Background
Stanniocalcins (STCs) represent small glycoprotein hormones, found in all vertebrates, which have been functionally implicated in Calcium homeostasis. However, recent data from mammalian systems indicated that they may be also involved in embryogenesis, tumorigenesis and in the context of the latter especially in angiogenesis. Human STC1 is a 247 amino acids protein with a predicted molecular mass of 27 kDa, but preliminary data suggested its di- or multimerization. The latter in conjunction with alternative splicing and/or post-translational modification gives rise to forms described as STC50 and "big STC", which molecular weights range from 56 to 135 kDa.

Results
In this study we performed a biochemical and structural analysis of STC1 with the aim of obtaining low resolution structural information about the human STC1, since structural information in this protein family is scarce. We expressed STC1 in both E. coli and insect cells using the baculo virus system with a C-terminal 6 × His fusion tag. From the latter we obtained reasonable amounts of soluble protein. Circular dichroism analysis showed STC1 as a well structured protein with 52% of alpha-helical content. Mass spectroscopy analysis of the recombinant protein allowed to assign the five intramolecular disulfide bridges as well as the dimerization Cys202, thereby confirming the conservation of the disulfide pattern previously described for fish STC1. SAXS data also clearly demonstrated that STC1 adopts a dimeric, slightly elongated structure in solution.

Conclusion
Our data reveal the first low resolution, structural information for human STC1. Theoretical predictions and circular dichroism spectroscopy both suggested that STC1 has a high content of alpha-helices and SAXS experiments revealed that STC1 is a dimer of slightly elongated shape in solution. The dimerization was confirmed by mass spectrometry as was the highly conserved disulfide pattern, which is identical to that found in fish STC1.
Transchromosomic cell model of Down syndrome shows aberrant migration, adhesion and proteome response to extracellular matrix
Authors: Delom Frédéric , Burt Emma , Hoischen Alex , Veltman Joris , Groet Jürgen , Cotter Finbarr E , Nizetic Dean 
Published: September 2009

Abstract

Background
Down syndrome (DS), caused by trisomy of human chromosome 21 (HSA21), is the most common genetic birth defect. Congenital heart defects (CHD) are seen in 40% of DS children, and >50% of all atrioventricular canal defects in infancy are caused by trisomy 21, but the causative genes remain unknown.

Results
Here we show that aberrant adhesion and proliferation of DS cells can be reproduced using a transchromosomic model of DS (mouse fibroblasts bearing supernumerary HSA21). We also demonstrate a deacrease of cell migration in transchromosomic cells independently of their adhesion properties. We show that cell-autonomous proteome response to the presence of Collagen VI in extracellular matrix is strongly affected by trisomy 21.

Conclusion
This set of experiments establishes a new model system for genetic dissection of the specific HSA21 gene-overdose contributions to aberrant cell migration, adhesion, proliferation and specific proteome response to collagen VI, cellular phenotypes linked to the pathogenesis of CHD.
Distribution and hormonal regulation of membrane progesterone receptors β and γ in ciliated epithelial cells of mouse and human fallopian tubes
Authors: Nutu Magdalena , Weijdegård Birgitta , Thomas Peter , Thurin-Kjellberg Ann , Billig Håkan , Larsson DG Joakim 
Published: September 2009

Abstract

Background
The controlled beating of cilia of the fallopian tube plays an important role in facilitating the meeting of gametes and subsequently transporting the fertilized egg to its implantation site. Rapid effects of progesterone on ciliary beat frequency have been reported in the fallopian tubes of cows, but the identity of the receptors mediating this non-genomic action of progesterone is not known. We recently identified a member of the non-genomic membrane progesterone receptor family, mPR gamma, as a candidate for mediating these actions of progesterone. Here, we investigated the possible presence of a related receptor, mPR beta, in the fallopian tubes of mice and women as well as the possible hormonal regulation of mPR beta and gamma.

Methods
Western blot and immunohistochemistry with specific antibodies were used to characterize the expression and cellular localization of the mPRs in mouse and human tissues. Taqman (Quantitative Polymerase Chain Reaction) assays were used to quantify mRNA levels in the fallopian tubes of two different mouse models after injections with different hormones and specific antagonists.

Results
In the fallopian tubes of both mouse and human, the expression of mPR beta and mPR gamma proteins was exclusively found in the ciliated cells. Whereas mPR beta was found on the cilia, mPR gamma was localized at the base of the same ciliated cells, as previously reported. In gonadotropin-primed mice, both mPRs genes were down-regulated after an injection with progesterone. Treatment with estradiol rapidly down-regulated the level of mPR beta mRNA and protein in immature mice. The mPR gamma protein was down-regulated around the time of ovulation in cycling women, similar to the regulation observed in mice stimulated to ovulate via gonadotropin injections.

Conclusion
Our findings show the presence and hormonal regulation of two distinct mPRs associated with the cilia of the fallopian tubes in both mice and women. It is hypothesized that these receptors are involved in the control of ciliary movement and, thus, gamete transport in the fallopian tubes of mammals.
Comparative structure analyses of cystine knot-containing molecules with eight aminoacyl ring including glycoprotein hormones (GPH) alpha and beta subunits and GPH-related A2 (GPA2) and B5 (GPB5) molecules
Authors: Alvarez Eva , Cahoreau Claire , Combarnous Yves 
Published: September 2009

Abstract

Background
Cystine-knot (cys-knot) structure is found in a rather large number of secreted proteins and glycoproteins belonging to the TGFbeta and glycoprotein hormone (GPH) superfamilies, many of which are involved in endocrine control of reproduction. In these molecules, the cys-knot is formed by a disulfide (SS) bridge penetrating a ring formed by 8, 9 or 10 amino-acid residues among which four are cysteine residues forming two SS bridges. The glycoprotein hormones Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), Thyroid-Stimulating Hormone (TSH) and Chorionic Gonadotropin (CG) are heterodimers consisting of non-covalently associated alpha and beta subunits that possess cys-knots with 8-amino-acyl (8aa) rings. In order to get better insight in the structural evolution of glycoprotein hormones, we examined the number and organization of SS bridges in the sequences of human 8-aa-ring cys-knot proteins having 7 (gremlins), 9 (cerberus, DAN), 10 (GPA2, GPB5, GPHα) and 12 (GPHβ) cysteine residues in their sequence.

Discussion
The comparison indicated that the common GPH-alpha subunit exhibits a SS bridge organization ressembling that of DAN and GPA2 but possesses a unique bridge linking an additional cysteine inside the ring to the most N-terminal cysteine residue. The specific GPHbeta subunits also exhibit a SS bridge organization close to that of DAN but it has two additional C-terminal cysteine residues which are involved in the formation of the "seat belt" fastened by a SS "buckle" that ensures the stability of the heterodimeric structure of GPHs. GPA2 and GPB5 exhibit no cys residue potentially involved in interchain SS bridge and GPB5 does not possess a sequence homologous to that of the seatbelt in GPH β-subunits. GPA2 and GPB5 are thus not expected to form a stable heterodimer at low concentration in circulation.

Summary
The 8-aa cys-knot proteins GPA2 and GPB5 are expected to form a heterodimer only at concentrations above 0.1 microM: this would be consistent with a short-term paracrine role but not with an endocrine role after dilution in circulation. Consequently, GPA2 and GPB5 could exert separate endocrine roles either during development and/or during adult life of both vertebrates and invertebrates.
Reflections on the United States Military 1941-1987
Authors: Mandels Mary , Eveleigh Douglas E 
Published: September 2009

Abstract
This article, 'Reflections on the United States Military 1941-1987' written by my grandmother, Mary Mandels, illustrates her passion for life. Her outreach article was considered most appropriate for publication in this forum. Her career activities are outlined in the prior article 'Mary Elizabeth Hickox Mandels, 90, Bioenergy Leader' while her accomplishments were fully recognized, for instance, nationally through the American Chemical Society and through her induction into the Hall of Fame at the US Army Soldier Systems Center in Natick, Massachusetts. As illustrated, along with Dr Elwyn Reese at Natick's Pioneering Research Laboratory, she headed a bioengineering group that is particularly remembered for developing a process for the enzymatic conversion of waste cellulosic biomass into soluble sugars that could be fermented to ethanol for an alternate liquid fuel (gasohol). This technology remains a subject of interest with growing environmental concerns and an oil shortage crisis.
Mary broke the promotional glass ceiling in her own field, all the more remarkable from the perspective that she was born 3 years before women gained the right to vote. Her talents as the family storyteller, enthralling her four siblings while growing up, later reflected her abilities as an outstanding mentor to young scientists. Mary's passions went beyond her career with a love of nature and the outdoors, taking frequent canoe, hiking, skiing, and camping trips. She had a broad fascination for science, foci including her encyclopedic knowledge of plants and wildlife. When not outdoors Mary enjoyed listening to music, from opera to 'Bobby' Dylan, as she called him. Her voracious appetite for books was apparent by the tomes that covered her coffee table. She was never shy to share her political opinions and would send long handwritten letters to politicians who did something to her disapproval. She was strong willed and passionate in everything that she did. In particular was her love of the nation and of the US Army, and this particular article reflects her passion. Mary was an inspiration to all of those who knew her. For me, she was not only my grandmother but also my friend and role model. I will forever miss her wisdom, spirit and passion for life.
Susan Roche
Appropriateness of hospitalization for CAP-affected pediatric patients: report from a Southern Italy General Hospital
Authors: Antonelli Fabio , De Brasi Daniele , Siani Paolo 
Published: September 2009

Abstract

Background
Community-acquired pneumonia (CAP) is a common disease, responsible for significant healthcare expenditures, mostly because of hospitalization. Many practice guidelines on CAP have been developed, including admission criteria, but a few on appropriate hospitalization in children. The aim of this study was to evaluate appropriate hospital admission for CAP in a pediatric population.

Methods
We evaluated appropriate admission to a Pediatric Unit performing a retrospective analysis on CAP admitted pediatric patients from a Southern Italy area. Diagnosis was made based on clinical and radiological signs. Appropriate hospital admission was evaluated following clinical and non-clinical international criteria. Family ability to care children was assessed by evaluating social deprivation status.

Results
In 2 winter seasons 120 pediatric patients aged 1-129 months were admitted because of CAP. Median age was 28.7 months. Raised body temperature was scored in 68.3% of patients, cough was present in 100% of cases, and abdominal pain was rarely evidenced. Inflammatory indices (ESR and CRP) were found elevated in 33.3% of cases. Anti-Mycoplasma pneumoniae antibodies were found positive in 20.4%. Trans-cutaneous (TC) SaO2 was found lower than 92% in 14.6%. Dyspnoea was present in 43.3%. Dehydration requiring i.v. fluid supplementation was scored in 13.3%. Evaluation of familial ability to care their children revealed that 76% of families (derived from socially depressed areas) were "at social risk", thus not able to appropriately care their children. Furthermore, analysis of CAP patients revealed that "at social risk" people accessed E.D. and were hospitalized more frequently than "not at risk" patients (odds ratio = 3.59, 95% CI: 1,15 to 11,12; p = 0.01), and that admitted "at social risk" people presented without clinical signs of severity (namely dyspnoea, and/or SaO2 ≤ 92%, and/or dehydration) more frequently than "not at risk" population (p = 0.005).

Conclusion
Dyspnoea was found to be the main clinical criterion to define an appropriate children admission for CAP. Other more objective evaluation (i.e. oxygen pulse oxymetry) could underestimate the necessity of hospitalization as patients discomfort could be more severe then indicated by TC SaO2. Furthermore, family inability to children care represents the main criterion for hospital admission in our geographic area. It reflects social deprivation status and it should be strongly considered in deciding for children hospital admission.
Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis
Authors: Sanmartí Raimon , Graell Eduard , Perez Maria L , Ercilla Guadalupe , Viñas Odette , Gómez-Puerta Jose A , Gratacós Jordi , Balsa Alejandro , Gómara Maria J , Larrosa Marta , Cañete Juan D , Haro Isabel 
Published: September 2009

Abstract
Introduction
Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA.

Methods
Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value.

Results
With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity.

Conclusions
CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression.
Early sensory relearning after median nerve repair using mirror training and sense substitution
Authors: Svens Birgit , Rosén Birgitta 
Published: September 2009

Background. The design and protocol of sensory re-education programmes has not changed over the last decades – a fact that may appear surprising when considering the enormous advances in neuroscience, cognitive science and brain imaging techniques that have increased our understanding of brain plasticity. A multitude of intrinsic and extrinsic factors influence the functional outcome after a nerve repair. Timing of when the sensory relearning is begun is one of them. Methods. Here we present a case following median nerve repair, where sensory re-education was introduced in the second week following surgery, i.e. long before any signs of nerve regeneration in the hand and fingers (Phase 1 sensory relearning). The aim was to activate and maintain the cortical hand representation areas for median nerve innervated parts of the hand. Mirror training and a new method with auditory input that substitute temporary missing sensory input were used. For evaluation, the Model Instrument for Outcome after Nerve Repair was utilized. Results. There was an improvement in overall score especially in the sensory domain of the Model Instrument for Outcome after Nerve Repair over the 25 months and this exceeded the upper limit of the 95% reference interval for an adult population. Conclusions. The excellent outcome in this case adds to other studies indicating that very early introduction of sensory relearning can greatly enhance the outcome following nerve repair.
James Hector (1834–1907): Doctor, geologist, explorer of Western Canada
Authors: Loosmore Brian 
Published: September 2009

Summary A graduate of the University of Edinburgh, James Hector joined the Palliser Expedition of 1857 as a doctor and geologist. The objectives of the expedition were to explore the plains of North America along the 49th parallel of latitude, the recently agreed boundary between the USA and Canada, and investigate passes through the Rocky Mountains for possible railway passage. Hector's contribution was immense, his dedication and endurance contributing in large measure to the success of the venture.