bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of functional polymorphisms in theTNFAgene in the pathogenesis of autoimmune thyroid diseases and production of anti-thyrotropin receptor antibody
Authors: Inoue N , Watanabe M , Nanba T , Wada M , Akamizu T , Iwatani Y 
Published: January 2009

SummaryThe severity of Hashimoto's disease (HD) and intractability of Graves' disease (GD) varies among patients. Severity of HD is associated with the functional +874A/T polymorphism for interferon-γ, an inflammatory cytokine. To clarify the association between functional polymorphisms in two other inflammatory cytokine genes [tumour necrosis factor (TNF)-α and interleukin (IL)-2] and the severity of autoimmune thyroid disease (AITD), we examined the TNF-α−1031T/C, TNF-α−857C/T and IL-2 −330T/G polymorphisms in genomic DNA samples. We genotyped 41 patients with intractable GD, 34 patients with GD in remission, 41 patients with severe HD, 36 patients with mild HD and 70 healthy controls. The frequency of carriers of TNF-α−1031C (CT + CC), which correlates with higher TNF-α production, was significantly higher in HD and GD patients than in controls, but was not associated with the severity of HD. In GD patients, the levels of anti-thyrotropin receptor antibody (TRAb) at onset of the disease was higher in patients with the TNF-α−857T (CT + TT) genotype, which correlates with higher TNF-α production, than in those with the −857CC genotype. We found no differences in the IL-2 −330T/G polymorphism among groups of AITD patients. In conclusion, the functional −1031T/C polymorphism of the TNFA gene is associated with the development of AITD and the functional −857C/T polymorphism is associated with the levels of TRAb in active GD patients.
Translating transplantation tolerance in the clinic: where are we, where do we go?
Authors: Goldman M , Wood K 
Published: January 2009

Summary
Research networks dedicated to translation of immune tolerance in the clinic currently support pilot trials aiming at immunosuppression withdrawal in kidney or liver allograft recipients. Although results obtained so far indicate that significant hurdles still need to be overcome before organ transplant recipients can be weaned off drugs safely and routinely, recent advances suggest that immunosuppression minimization on the basis of validated biomarkers might become standard practice in a near future.
Immune characterization of an individual with an exceptionally high natural killer T cell frequency and her immediate family
Authors: Chan A C , Serwecinska L , Cochrane A , Harrison L C , Godfrey D I , Berzins S P 
Published: January 2009

Summary
Natural killer T cells (NKT) are a regulatory subset of T lymphocytes whose frequency in peripheral blood is highly variable within the human population. Lower than normal NKT frequencies are associated with increased predisposition to a number of diseases, including type 1 diabetes and some forms of cancer, raising the possibility that an increased frequency may be protective. However, there is little or no understanding of how high NKT frequencies arise or, most importantly, whether the potential exists to boost and maintain NKT levels for therapeutic advantage. Here, we provide a detailed functional and phenotypic characterization of the NKT compartment of a human donor with NKT levels approximately 50 times greater than normal, including an analysis of NKT in her immediate family members. The study focuses upon the characteristics of this donor and her family, but demonstrates more broadly that the size and flexibility of the NKT niche is far greater than envisioned previously. This has important implications for understanding how the human NKT compartment is regulated, and supports the concept that the human NKT compartment might be expanded successfully for therapeutic benefit.
Tel2: a common partner of PIK‐related kinases and a link between DNA checkpoint and nutritional response?
Authors: Kanoh Junko , Yanagida Mitsuhiro 
Published: January 2009

A recent paper (Hayashi et al. 2007) in this issue of Genes to Cells shows that the fission yeast Schizosaccharomyces pombe Tel2, a homologue of mammalian/worm CLK2/Clk‐2/Rad‐5, physically interacts with all the phosphoinositide 3‐kinase‐related kinases (PIKKs) that include Rad3/Tel1 (ATR/ATM homologues), Tor1/Tor2 (TOR kinases) and Tra1/Tra2 (TRRAP homologues), raising the possibility that Tel2 family proteins link various PIKK‐related cellular processes by interacting with PIKK family proteins. In this minireview, implications and impact of the findings, and a possibility that PIKKs are functionally related through Tel2, are discussed.
Ribosomal stress induces processing of Mybbp1a and its translocation from the nucleolus to the nucleoplasm
Authors: Yamauchi Tomohiro , Keough Rebecca A. , Gonda Thomas J. , Ishii Shunsuke 
Published: January 2009

Myb‐binding protein 1a (Mybbp1a) was originally identified as a c‐myb proto‐oncogene product (c‐Myb)‐interacting protein, and also binds to various other transcription factors. The 160‐kDa Mybbp1a protein (p160MBP) is ubiquitously expressed and is post‐translationally processed in some types of cells to generate an amino‐terminal 67 kDa fragment (p67MBP). Despite its interaction with various transcription factors, Mybbp1a is localized predominantly, but not exclusively, in nucleoli. Here, we have purified the two Mybbp1a‐containing complexes. The smaller complex contained p67MBP and p140MBP, which lacked the C‐terminal region of p160MBP containing the nucleolar localization sequences. The larger complex contained the intact p160MBP and various ribosomal subunits. Treatment of cells with actinomycin D (ActD), cisplatin or UV, all of which inhibit ribosome biogenesis, induced processing of p160MBP into p140MBP and p67MBP. ActD, cisplatin and UV also induced a translocation of Mybbp1a from the nucleolus to the nucleoplasm. Both small and large Mybbp1a complexes contained nucleophosmin and nucleolin. In contrast, nucleostemin was detected only in the large complex, while the cell cycle‐regulated protein EBP1 was only in the small complex. These results suggest that Mybbp1a may connect the ribosome biogenesis and the Myb‐dependent transcription, which controls cell cycle progression and proliferation.
Quantifying photosynthetic capacity and its relationship to leaf nitrogen content for global‐scale terrestrial biosphere models
Authors: KATTGE JENS , KNORR WOLFGANG , RADDATZ THOMAS , WIRTH CHRISTIAN 
Published: January 2009

AbstractPhotosynthetic capacity and its relationship to leaf nitrogen content are two of the most sensitive parameters of terrestrial biosphere models (TBM) whose representation in global‐scale simulations has been severely hampered by a lack of systematic analyses using a sufficiently broad database. Here, we use data of qualitative traits, climate and soil to subdivide the terrestrial vegetation into functional types (PFT), and then assimilate observations of carboxylation capacity, Vmax (723 data points), and maximum photosynthesis rates, Amax (776 data points), into the C3 photosynthesis model proposed by Farquhar et al. to constrain the relationship of (Vmax normalised to 25 °C) to leaf nitrogen content per unit leaf area for each PFT. In a second step, the resulting functions are used to predict per PFT from easily measurable values of leaf nitrogen content in natural vegetation (1966 data points). Mean values of thus obtained are implemented into a TBM (BETHY within the coupled climate–vegetation model ECHAM5/JSBACH) and modelled gross primary production (GPP) is compared with independent observations on stand scale. Apart from providing parameter ranges per PFT constrained from much more comprehensive data, the results of this analysis enable several major improvements on previous parameterisations. (1) The range of mean between PFTs is dominated by differences of photosynthetic nitrogen use efficiency (NUE, defined as divided by leaf nitrogen content), while within each PFT, the scatter of values is dominated by the high variability of leaf nitrogen content. (2) We find a systematic depression of NUE on certain tropical soils that are known to be deficient in phosphorous. (3) of tropical trees derived by this study is substantially lower than earlier estimates currently used in TBMs, with an obvious effect on modelled GPP and surface temperature. (4) The root‐mean‐squared difference between modelled and observed GPP is substantially reduced.
Drought turns a Central European Norway spruce forest soil from an N2O source to a transient N2O sink
Authors: GOLDBERG STEFANIE DANIELA , GEBAUER GERHARD 
Published: January 2009

AbstractBased on current climate scenarios, a higher frequency of summer drought periods followed by heavy rainfall events is predicted for Central Europe. It is expected that drying/rewetting events induce an increased matter cycling in soils and may contribute considerably to increased emissions of the greenhouse gas N2O on annual scales. To investigate the influence of drying/rewetting events on N2O emissions in a mature Norway spruce forest in the Fichtelgebirge area (NE Bavaria, Germany), a summer drought period of 46 days was induced by roof installations on triplicate plots, followed by a rewetting event of 66 mm experimental rainfall in 2 days. Three nonmanipulated plots served as controls. The experimentally induced soil drought was accompanied by a natural drought. During the drought period, the soil of both the throughfall exclusion and control plots served as an N2O sink. This was accompanied by subambient N2O concentrations in upper soil horizons. The sink strength of the throughfall exclusion plots was doubled compared with the control plots. We conclude that the soil water status together with the soil nitrate availability was an important driving factor for the N2O sink strength. Rewetting quickly turned the soil into a source for atmospheric N2O again, but it took almost 4 months to turn the cumulative soil N2O fluxes from negative (sink) to positive (source) values. N2O concentration and isotope analyses along soil profiles revealed that N2O produced in the subsoil was subsequently consumed during upward diffusion along the soil profile throughout the entire experiment. Our results show that long drought periods can lead to drastic decreases of N2O fluxes from soils to the atmosphere or may even turn forest soils temporarily to N2O sinks. Accumulation of more field‐scale data on soil N2O uptake as well as a better understanding of underlying mechanisms would essentially advance our knowledge of the global N2O budget.
Threonine phosphorylation prevents promoter DNA binding of the Group B Streptococcus response regulator CovR
Authors: Lin Wan‐Jung , Walthers Don , Connelly James E. , Burnside Kellie , Jewell Kelsea A. , Kenney Linda J. , Rajagopal Lakshmi 
Published: January 2009

SummaryAll living organisms communicate with the external environment for their survival and existence. In prokaryotes, communication is achieved by two‐component systems (TCS) comprising histidine kinases and response regulators. In eukaryotes, signalling is accomplished by serine/threonine and tyrosine kinases. Although TCS and serine/threonine kinases coexist in prokaryotes, direct cross‐talk between these families was first described in Group B Streptococcus (GBS). A serine/threonine kinase (Stk1) and a TCS (CovR/CovS) co‐regulate toxin expression in GBS. Typically, promoter binding of regulators like CovR is controlled by phosphorylation of the conserved active site aspartate (D53). In this study, we show that Stk1 phosphorylates CovR at threonine 65. The functional consequence of threonine phosphorylation of CovR in GBS was evaluated using phosphomimetic and silencing substitutions. GBS encoding the phosphomimetic T65E allele are deficient for CovR regulation unlike strains encoding the non‐phosphorylated T65A allele. Further, compared with wild‐type or T65A CovR, the T65E CovR is unable to bind promoter DNA and is decreased for phosphorylation at D53, similar to Stk1‐phosphorylated CovR. Collectively, we provide evidence for a novel mechanism of response regulator control that enables GBS (and possibly other prokaryotes) to fine‐tune gene expression for environmental adaptation.
A life without pain? Hedonists take note
Authors: Young FBJ 
Published: January 2009

An SCN9A channelopathy causes congenital inability to experience pain Cox et al. (2006) Nature 444: 894–898Loss‐of‐function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations Goldberg et al. (2007) Clin Genet 71: 311–319A stop codon mutation in SCN9A causes lack of pain sensation Ahmad et al. (2007) Hum Mol Genet 16: 2114–2121‘We cannot learn without pain.’– Aristotle
RPGRIP1: a novel ciliary gene involved in cerebellar disorders
Authors: Karasinska JM 
Published: January 2009

The ciliary gene RPGRIP1L is mutated in cerebello‐oculo‐renal syndrome (Joubert syndrome type B) and Meckel syndrome Delous et al. (2007) Nature Genetics 39: 875–881Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin interactor, cause Joubert syndrome Arts et al. (2007) Nature Genetics 39: 882–888
Loss of dynamic histone regulation underlies mental retardation
Authors: Grant ME 
Published: January 2009

The X‐linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases Iwase et al. (2007) Cell 128: 1077–1088The histone H3K4 demethylase SMCX links REST target genes to X‐linked mental retardation Tahiliani et al. (2007) Nature 447: 601–606
The genetic basis of uric acid variance
Authors: Stein RA 
Published: January 2009

SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout Vitart et al. (2008) Nature Genetics 40(4): 437–442SLC2A9 influences uric acid concentrations with pronounced sex‐specific effects Döring et al. (2008) Nature Genetics 40(4): 430–436
Impact of a regional anesthesia rotation on ultrasonographic identification of anatomic structures by anesthesiology residents
Authors: OREBAUGH S. L. , BIGELEISEN P. E. , KENTOR M. L. 
Published: January 2009

Objective: The specific aim of this study was to determine the ability of anesthesiology residents to independently identify a series of anatomic structures in a live model using ultrasound, both before and after a 4‐week regional anesthesia rotation that incorporates a standardized ultrasound training curriculum for peripheral nerve blockade.Methods: Ten CA2 and CA3 anesthesiology residents volunteered to participate in this study. Each resident was subjected to a pre‐rotation practical exam, in which he attempted to identify 15 structures at four sites of peripheral nerve blockade, in a test subject. Each resident then received specific training for ultrasound‐guided nerve blocks during a 4‐week regional anesthesia rotation, and then completed a post‐rotation exam. The mean number of structures correctly identified on the exams was compared for significant differences utilizing a paired t‐test.Results: Residents were able to identify significantly more anatomic structures on the post‐rotation exam as compared with the pre‐rotation exam (mean 14.1 vs. 9.9, P<.001), as well as more peripheral nerve targets. The most frequently misidentified structures on the pre‐rotation exam were the subclavian vein, the sciatic nerve in the popliteal fossa, and the femur.Conclusions: Ultrasound‐naïve anesthesiology residents, who received instruction and experience with ultrasound‐guided peripheral nerve blocks on a 4‐week regional anesthesia rotation, significantly improved their ability to independently identify relevant anatomic structures with ultrasonography.
Equal effects of gelatin and hydroxyethyl starch (6% HES 130/0.42) on modified thrombelastography in children
Authors: OSTHAUS W. A. , WITT L. , JOHANNING K. , BOETHIG D. , WINTERHALTER M. , HUBER D. , HEIMBUCHER C. , SUEMPELMANN R. 
Published: January 2009

Background: Artificial colloids are frequently used to prevent or treat circulatory failure due to hypovolaemia. Whereas gelatin has been shown not to affect coagulation besides its haemodilutional effect, hydroxyethyl starches (HES) have additional negative effects on haemostasis. The third‐generation HES solutions have been developed to minimise these effects. We therefore conducted a prospective, randomised study, to verify the hypothesis that a 6% HES 130/0.42/6 : 1 and a 4% gelatin infusion influences modified thrombelastography (TEM) parameters in children in the same manner and to the same extent.Methods: A total of 50 paediatric patients aged 0–12 years scheduled for surgery were assigned to receive either 10 ml/kg HES 130/0.42 or gelatin. Blood gas analysis, haemodynamic parameters and TEM measurements were performed before and after colloid administration.Results: Patient characteristics, indications/surgical procedures and the main results obtained from blood gas analysis were comparable between the two groups. After administration of either gelatin or HES, all TEM parameters, except for clotting time, indicated impaired coagulation whereas the mean values of all TEM parameters remained within the normal ranges. Comparing the gelatin and HES 130/0.42/6 : 1 groups, none of the measured TEM parameters was found to show between‐group differences at baseline or after colloid infusion.Conclusion: In conclusion, we could demonstrate that the investigational product, HES 130/0.42/6 : 1 solution, administered at a dosage of 10 ml/kg to children, had comparable effects on coagulation monitored with TEM as a gelatin solution. Perioperative administration of HES 130/0.42/6 : 1 does not alter coagulation to an extent above and beyond the effect of haemodilution.
Living without aprotinin: the results of a 5‐year blood saving program in cardiac surgery
Authors: RANUCCI M. , CASTELVECCHIO S. , ROMITTI F. , ISGRÒ G. , BALLOTTA A. , CONTI D. 
Published: January 2009

Background: After 20 years of regular use in cardiac surgery patients, aprotinin has recently been withdrawn from the market due to many concerns about its safety. For a number of reasons aprotinin has not been available in Italy since 1998. The present study presents an aprotinin‐free treatment protocol applied at our institution during the last 5 years, and aims to verify the results of this protocol in terms of allogeneic blood product transfusions, postoperative blood loss and surgical re‐exploration rate.Methods: Retrospective study on 7988 consecutive patients who underwent cardiac surgery during the years 2003–2007. All the patients received specific hemostasis/coagulation management based on (a) routine use of tranexamic acid, (b) heparin dose–response monitoring, thromboelastography, platelet (PLT) function analysis in a select population of patients, and (c) use of fresh frozen plasma (FFP), PLTs, and desmopressin according to the hemostasis/coagulation profile. Data retrieved from the institutional database were quantity of packed red cells (PRCs), FFP, PLT transfusion rate, blood loss in the first 12 postoperative hours, and surgical re‐exploration rate.Results: PRCs were transfused in 40.4% of patients (with higher rates for selected high‐risk subpopulations), FFP in 12.9% and PLTs in 2.6%. Surgical re‐exploration rate was 3.7%. With respect to historical controls, a significant reduction of PRCs and FFP transfusions was obtained using closed circuits, point of care coagulation tests, and combination of the two.Conclusion: This aprotinin‐free blood saving program is an effective strategy for allogeneic blood products transfusion containment.
Glycomolecule Modifications in the Seminiferous Epithelial Cells and in the Acrosome of Post‐testicular Spermatozoa in the Alpaca
Authors: Parillo F , Verini Supplizi A , Mancuso R , Catone G 
Published: January 2009

ContentsA lectin histochemical investigation of the seminiferous epithelium and acrosomes of spermatozoa present in the efferent ductules and epididymal regions was carried out in the alpaca. The histochemical characterization was performed using a battery of different lectins: Con‐A, UEA‐I, LTA, WGA, GSA‐IB4, SBA, PNA, ECA, DBA, MAL‐II and SNA. Sialidase digestion and deglycosilation pre‐treatments were also employed. The cytoplasm of the Sertoli cells contained N‐linked oligosaccharides with α‐d‐Man/α‐d‐Glc and GlcNAc and O‐linked glycans with α‐l‐Fuc, β‐GalNAc, β‐d‐Gal‐(1‐4)‐d‐GlcNAc, α–Gal and Neu5Acα2,6α‐GalNAc moieties whereas β‐d‐Gal‐(1‐3)‐d‐GalNAc residues were included in both O‐ and N‐glycoproteins. Spermatogonia expressed α‐d‐Man/α‐d‐Glc residues included in N‐glycoproteins and α‐Fuc in O‐glycoproteins. Spermatocytes contained the N‐glycoproteins residues α‐d‐Man/α‐d‐Glc and GlcNAc and the O‐glycoproteins residues α‐l‐Fuc, β‐d‐Gal‐(1‐4)‐d‐GlcNAc, α–Gal, β‐GalNAc, Neu5Acα2,6α‐GalNAc and Neu5Acα2,6β‐d‐Gal‐(1‐3)‐d‐GalNAc. The results of the present study show differences in the presence and distribution of lectin reactive sites throughout the acrosomal development in the alpaca. In particular, Fuc moieties were found only during the Golgi‐phase of spermatids, α‐Gal were found in the acrosome of Golgi‐ and cap‐phase spermatids, sialic‐acid/α‐GalNAc sequence was revealed during the cap‐phase and elongated spermatids, and α‐d‐Man/α‐d‐Glc and GlcNAc were detected only in the acrosomes of elongated spermatids. Finally, β‐GalNAc, β‐d‐Gal‐(1‐3)‐d‐GalNAc and β‐d‐Gal‐(1‐4)‐d‐GlcNAc were added to acrosomal glycoproteins in the early stages of spermatogenesis and remained unchanged during the later phases. Differences in the carbohydrate expression were also demonstrated on the sperm acrosomes during passage through the post‐testicular ducts.
Impact of rurality on environmental determinants and hazards
Authors: Veitch Craig 
Published: January 2009

Abstract The original of this paper was prepared as invited pre‐reading for the Inaugural Rural Health Symposium held in Brisbane in July 2008 under the theme ‘The impact of “rurality” ’, sub‐theme (a) Environmental determinants. The natural environment shapes human activity, both economically and socially. It also directly and indirectly influences health and well‐being. People in rural and remote areas are more directly exposed to the natural environment than their urban counterparts. The built environment is largely a product of economic activity; thus, the built environment in rural areas tends to reflect the predominant primary industry/ies. The rural built environment presents many potential hazards and risks to health and well‐being, particularly for those involved in the primary industries, which are either not present in urban areas, or are present on smaller or more contained scales. The natural and built environments also influence individuals' attitudes and behaviours, both positively and negatively. The environmental determinants of rural health, therefore, can be considered in terms of the natural environment, the built environment and individuals' responses to environmental influences. This paper raises some of the common environmental determinants of rural health and well‐being and briefly touches on what these mean for rural health service delivery.
Integration and coordination of care
Authors: Dunbar James , Reddy Prasuna 
Published: January 2009

Abstract The health care systems in Australia are under pressure from workforce shortages, increasing costs and an ageing population with a high prevalence of chronic disease. There is a well‐established description of inequity in health outcomes among rural and remote populations. Most of the inequity appears to be due to poorer access to services than higher levels of health risk factors, such as cholesterol, blood pressure or obesity. Over the last 15 years, the science of improvement has led to quality improvement techniques, such as collaboratives, managed clinical networks and collaborative care, all of which have been tried successfully in Australia. Each of these offers ways to reduce the inequity in health outcomes attributed to rurality or remoteness.