bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional and Metabolic Adjustments in ADP-Glucose Pyrophosphorylase-Deficientbt2Maize Kernels
Authors: Cossegal Magalie , Chambrier Pierre , Mbelo Sylvie , Balzergue Sandrine , Martin-Magniette Marie-Laure , Moing Annick , Deborde Catherine , Guyon Virginie , Perez Pascual , Rogowsky Peter 
Published: February 2008

AbstractDuring the cloning of monogenic recessive mutations responsible for a defective kernel phenotype in a Mutator-induced Zea mays mutant collection, we isolated a new mutant allele in Brittle2 (Bt2), which codes for the small subunit of ADP-glucose pyrophosphorylase (AGPase), a key enzyme in starch synthesis. Reverse transcription-polymerase chain reaction experiments with gene-specific primers confirmed a predominant expression of Bt2 in endosperm, of Agpsemzm in embryo, and of Agpslzm in leaf, but also revealed considerable additional expression in various tissues for all three genes. Bt2a, the classical transcript coding for a cytoplasmic isoform, was almost exclusively expressed in the developing endosperm, whereas Bt2b, an alternative transcript coding for a plastidial isoform, was expressed in almost all tissues tested with a pattern very similar to that of Agpslzm. The phenotypic analysis showed that, at 30 d after pollination (DAP), mutant kernels were plumper than wild-type kernels, that the onset of kernel collapse took place between 31 and 35 DAP, and that the number of starch grains was greatly reduced in the mutant endosperm but not the mutant embryo. A comparative transcriptome analysis of wild-type and bt2-H2328 kernels at middevelopment (35 DAP) with the 18K GeneChip Maize Genome Array led to the conclusion that the lack of Bt2-encoded AGPase triggers large-scale changes on the transcriptional level that concern mainly genes involved in carbohydrate or amino acid metabolic pathways. Principal component analysis of 1H nuclear magnetic resonance metabolic profiles confirmed the impact of the bt2-H2328 mutation on these pathways and revealed that the bt2-H2328 mutation did not only affect the endosperm, but also the embryo at the metabolic level. These data suggest that, in the bt2-H2328 endosperms, regulatory networks are activated that redirect excess carbon into alternative biosynthetic pathways (amino acid synthesis) or into other tissues (embryo).
The structure of the lipid‐embedded potassium channel voltage sensor determined by double‐electron–electron resonance spectroscopy
Authors: Vamvouka Magdalini , Cieslak John , Van Eps Ned , Hubbell Wayne , Gross Adrian 
Published: February 2008

AbstractA four‐pulse electron paramagnetic resonance experiment was used to measure long‐range inter‐subunit distances in reconstituted KvAP, a voltage‐dependent potassium (Kv) channel. The measurements have allowed us to reach the following five conclusions about the native structure of the voltage sensor of KvAP. First, the S1 helix of the voltage sensor engages in a helix packing interaction with the pore domain. Second, the crystallographically observed antiparallel helix‐turn‐helix motif of the voltage‐sensing paddle is retained in the membrane‐embedded voltage sensor. Third, the paddle is oriented in such a way as to expose one face to the pore domain and the opposite face to the membrane. Fourth, the paddle and the pore domain appear to be separated by a gap that is sufficiently wide for lipids to penetrate between the two domains. Fifth, the critical voltage‐sensing arginine residues on the paddle appear to be lipid exposed. These results demonstrate the importance of the membrane for the native structure of Kv channels, suggest that lipids are an integral part of their native structure, and place the voltage‐sensing machinery into a complex lipid environment near the pore domain.
Structural constraints on autoprocessing of the human nucleoporin Nup98
Authors: Sun Yixin , Guo Hwai‐Chen 
Published: February 2008

AbstractNucleoporin Nup98, a 98‐kDa protein component of the nuclear pore complex, plays an important role in both protein and RNA transport. During its maturation process, Nup98 undergoes post‐translational autoproteolysis, which is critical for targeting to the NPC. Here we present high‐resolution crystal structures of the C‐terminal autoproteolytic domains of Nup98 (2.3 Å for the wild type and 1.9 Å for the S864A precursor), and propose a detailed autoproteolysis mechanism through an N–O acyl shift. Structural constraints are found at the autocleavage site, and could thus provide a driving force for autocleavage at the scissile peptide bond. Such structural constraints appear to be generated, at least in part, by anchoring a conserved phenylalanine side chain into a highly conserved hydrophobic pocket at the catalytic site. Our high‐resolution crystal structures also reveal that three highly conserved residues, Tyr866, Gly867, and Leu868, provide most of the interactions between the autoproteolytic domain and the C‐terminal tail. These results suggest that Nup98 may represent a new subtype of protein that utilizes autoprocessing to control biogenesis pathways and intracellular translocation.
Crystal structure of LpxC from Pseudomonas aeruginosa complexed with the potent BB‐78485 inhibitor
Authors: Mochalkin Igor , Knafels John D. , Lightle Sandra 
Published: February 2008

AbstractThe cell wall in Gram‐negative bacteria is surrounded by an outer membrane comprised of charged lipopolysaccharide (LPS) molecules that prevent entry of hydrophobic agents into the cell and protect the bacterium from many antibiotics. The hydrophobic anchor of LPS is lipid A, the biosynthesis of which is essential for bacterial growth and viability. UDP‐3‐O‐(R‐3‐hydroxymyristoyl)‐N‐acetylglucosamine deacetylase (LpxC) is an essential zinc‐dependant enzyme that catalyzes the conversion of UDP‐3‐O‐(R‐3‐hydroxymyristoyl)‐N‐acetylglucosamine to UDP‐3‐O‐(R‐3‐hydroxymyristoyl)glucosamine and acetate in the biosynthesis of lipid A, and for this reason, LpxC is an attractive target for antibacterial drug discovery. Here we disclose a 1.9 Å resolution crystal structure of LpxC from Pseudomonas aeruginosa (paLpxC) in a complex with the potent BB‐78485 inhibitor. To our knowledge, this is the first crystal structure of LpxC with a small‐molecule inhibitor that shows antibacterial activity against a wide range of Gram‐negative pathogens. Accordingly, this structure can provide important information for lead optimization and rational design of the effective small‐molecule LpxC inhibitors for successful treatment of Gram‐negative infections.
Use of a sparse sampling study design to assess transfer of tramadol and its O‐desmethyl metabolite into transitional breast milk
Authors: Ilett Kenneth F. , Paech Michael J. , Page‐Sharp Madhu , Sy Sherwin K. , Kristensen Judith H. , Goy Raymond , Chua Sebastian , Christmas Tracey , Scott Karen L. 
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • There are presently no published data on tramadol transfer into breast milk or on its effects in the breastfed infant. WHAT THIS STUDY ADDS • We have provided quantitative data on the absolute and relative infant doses of rac‐tramadol and it rac‐O‐desmethyl metabolite for the breastfed infant.• We have also demonstrated a novel sparse sampling data collection method for investigating infant exposure via milk.AIMSTo investigate the transfer of rac‐tramadol and its rac‐O‐desmethyl metabolite into transitional milk, and assess unwanted effects in the breastfed infant.METHODSTramadol HCl (100 mg six hourly) was administered to 75 breastfeeding mothers for postoperative analgesia on days 2–4 after Caesarian section. Milk and plasma samples were collected after administration of four or more doses. Rac‐tramadol and rac‐O‐desmethyltramadol were measured by high performance liquid chromatography. Milk : plasma ratio (M : P) and infant doses were calculated by standard methods. The behavioural characteristics of the exposed breastfed infants and a matched control group of infants not exposed to tramadol were also studied.RESULTSAt steady‐state, mean (95% CI) M : P was 2.2 (2.0, 2.4) for rac‐tramadol and 2.8 (2.5, 3.1) for rac‐O‐desmethyltramadol. The estimated absolute and relative infant doses were 112 (102, 122) μg kg−1 day−1 and 30 (28, 32) μg kg−1 day−1, and 2.24% (2.04, 2.44)% and 0.64% (0.59, 0.69)% for rac‐tramadol and rac‐O‐desmethyltramadol, respectively. The exposed infants and control breastfed infants had similar characteristics, including Apgar scores at birth and Neurologic and Adaptive Capacity Scores.CONCLUSIONSThe combined relative infant dose of 2.88% at steady‐state was low. The similarity of NACS in exposed infants and controls suggests that there were no significant behavioural adverse effects. We conclude that short‐term maternal use of tramadol during establishment of lactation is compatible with breastfeeding.
Fludarabine‐based cytoreductive regimen and T‐cell‐depleted grafts from alternative donors for the treatment of high‐risk patients with Fanconi anaemia
Authors: Chaudhury Sonali , Auerbach Arleen D. , Kernan Nancy A. , Small Trudy N. , Prockop Susan E. , Scaradavou Andromachi , Heller Glenn , Wolden Suzanne , O’Reilly Richard J. , Boulad Farid 
Published: February 2008

SummaryEighteen consecutive patients aged 5·5–24 years with Fanconi anaemia and diagnoses of aplastic anaemia (n = 8), myelodysplastic syndrome (n = 4), acute myeloid leukaemia (n = 6), received allogeneic haematopoietic stem cell transplants from alternative donors. All patients had been transfused, 13 had previously been treated with androgens and 14 had a history of infection. Donors were related human leucocyte antigen (HLA) mismatched for eight patients, unrelated HLA mismatched for seven patients and unrelated HLA matched for three patients. Cytoreduction included single dose total body irradiation (450 cGy), fludarabine (150 mg/m2) and cyclophosphamide (40 mg/kg). Immunosuppression included antithymocyte globulin and tacrolimus. Grafts were granulocyte colony‐stimulating factor‐mobilized, CD34+ T‐cell‐depleted peripheral blood stem cells in 15 patients and T‐cell‐depleted marrows in three. All 18 patients engrafted with 100% donor chimaerism; only one patient developed graft‐versus‐host disease (GVHD). With a median follow‐up of 4·2 years, 13/18 patients were alive, 12 of these were disease‐free. Five‐year overall survival and disease‐free survival were 72·2% and 66·6% respectively. Immune reconstitution was achieved at approximately 6 months post‐transplant for most patients. These are encouraging results of T‐cell‐depleted transplants from alternative donors using fludarabine‐based cytoreduction in 18 high‐risk patients with Fanconi anaemia, with no evidence of rejection and minimal GVHD.
Alcohol consumption and the risk of self‐reported perennial and seasonal allergic rhinitis in young adult women in a population‐based cohort study
Authors: Bendtsen P. , Grønbæk M. , Kjær S. K. , Munk C. , Linneberg A. , Tolstrup J. S. 
Published: February 2008

SummaryBackgroundAlcohol consumption has been suggested to be associated with the development of allergic rhinitis (AR), but there is limited data on the topic.ObjectivesThe objective of this study was to investigate the association between alcohol consumption and the risk of developing AR among young women.MethodsFive thousand eight hundred and seventy Danish women aged 20–29 years participated in a prospective cohort study, and were free of seasonal and perennial AR at baseline (1991–1993). Alcohol consumption was assessed by a food frequency questionnaire. The main outcome measures were self‐reported information on seasonal and perennial AR debuting during a mean follow‐up period of 7.8 years.ResultsDuring follow‐up, 831 women developed seasonal AR and 523 women developed perennial AR, corresponding to 14% and 9%. Alcohol consumption was positively associated with the risk of developing perennial AR. The adjusted odds ratio (OR) for perennial AR was 1.78 (95% CI, 1.13–2.80) among women drinking more than 14 drinks/week compared with women drinking <1 drink/week. There was no association between alcohol consumption and seasonal AR. Having one or two parents with asthma was, after adjustment, significantly associated with the risk of developing seasonal (OR, 2.01; 95% CI, 1.65–2.45) and perennial AR (OR, 2.28; 95% CI, 1.70–2.74). Smoking was not associated with an increased risk of developing AR.ConclusionIn this population of young adult women, alcohol consumption was associated with an increased risk of developing perennial AR.
Effect of ripeness at processing on fresh‐cut ‘Flor de Invierno’ pears packaged under modified atmosphere conditions
Authors: Oms‐Oliu Gemma , Aguiló‐Aguayo Ingrid , Soliva‐Fortuny Robert , Martín‐Belloso Olga 
Published: February 2008

SummaryThe effects of ripeness at processing and packaging conditions on respiration, microbiological stability as well as colour and firmness of fresh‐cut ‘Flor de Invierno’ pears were evaluated throughout storage. Although a 2.5‐kPa O2 + 7‐kPa CO2 atmosphere led to an inhibition of ethylene synthesis and carbon dioxide production compared with non‐modified atmosphere packaging, the more advanced the ripeness stage at processing, the higher the physiological activity and thus, the higher production of carbon dioxide, ethylene and ethanol. A 2.5‐kPa O2 + 7‐kPa CO2 atmosphere inhibited bacterial growth, yeast and mould proliferation in mature‐green pears but fast microbial growth was observed especially on ripe pears, under both packaging conditions. In conclusion, the shelf‐life of ripe pears was reduced by increased respiration response to processing and accelerated microbial spoilage. Instead, pears processed in a partially ripe stage were suitable for conservation while gathering desired sensory attributes. Therefore, for commercial purposes, a shelf‐life of 10 days was suggested for partially ripe fresh‐cut pears packaged under a 2.5‐kPa O2 + 7‐kPa CO2 atmosphere.
Caustic‐induced gelation of β‐lactoglobulin
Authors: Mercadé‐Prieto Ruben , Paterson William R. , Ian Wilson D. 
Published: February 2008

SummaryThe gelation kinetics of β‐lactoglobulin (βLg) solutions has been determined in the alkaline regime over a wide range of protein concentrations, gelling temperatures and gelation pH (pHgel), set using NaOH. The behaviour is compared with caustic‐induced gelation of whey protein concentrate and the alkaline dissolution of heat‐induced whey gels. The gelation time decreases significantly between neutral conditions and pHgel 9, because of the activation of the free cysteine groups and displacement to the monomeric form, and between pHgel 10 and 11, due to the base denaturation of βLg. Both transitions are associated with a significant decrease in the activation energy of gelation. At pHgel >11.5 the gelation time is observed to increase with pHgel, owing to destruction of interprotein crosslinks. These results are consistent with the recently reported observation that a minimum pH for the dissolution of βLg gels and aggregates exists around 11.6 [Biomacromolecules8 (2007) 1162]. This phenomenon has been assigned to the destruction of non‐covalent interactions that would inhibit the final percolation of the gel.
The metabolic syndrome as a tool for predicting future diabetes: the AusDiab study
Authors: Cameron A. J. , Magliano D. J. , Zimmet P. Z. , Welborn T. A. , Colagiuri S. , Tonkin A. M. , Shaw J. E. 
Published: February 2008

Abstract.Objective.  To compare the ability of the metabolic syndrome (MetS), a diabetes prediction model (DPM), a noninvasive risk questionnaire and individual glucose measurements to predict future diabetes.Design.  Five‐year longitudinal cohort study. Tools tested included MetS definitions [World Health Organization, International Diabetes Federation, ATPIII and European Group for the study of Insulin Resistance (EGIR)], the FINnish Diabetes RIsk SCore risk questionnaire, the DPM, fasting and 2‐h post load plasma glucose.Setting.  Adult Australian population.Subjects.  A total of 5842 men and women without diabetes ≥25 years. Response 58%. A total of 224 incident cases of diabetes.Results.  In receiver operating characteristic curve analysis, the MetS was not a better predictor of incident diabetes than the DPM or measurement of glucose. The risk for diabetes among those with prediabetes but not MetS was almost triple that of those with MetS but not prediabetes (9.0% vs. 3.4%). Adjusted for component parts, the MetS was not a significant predictor of incident diabetes, except for EGIR in men [OR 2.1 (95% CI 1.2–3.7)].Conclusions.  A single fasting glucose measurement may be more effective and efficient than published definitions of the MetS or other risk constructs in predicting incident diabetes. Diagnosis of the MetS did not confer increased risk for incident diabetes independent of its individual components, with an exception for EGIR in men. Given these results, debate surrounding the public health utility of a MetS diagnosis, at least for identification of incident diabetes, is required.
Neurogenesis and Depression: Breakthrough or Blind Alley?
Authors: Herbert Joe 
Published: February 2008

SummaryPieces of evidence are emerging in support of the startling idea that the birth of new neurones in the adult brain in some way underlies major depression. Although there are intriguing parallels between factors that regulate neurogenesis and those predicting depression or its recovery, at this point, we should remain sceptical but allow cautious hope that more effective therapies may be suggested.
Evidence for human‐mediated dispersal of exotic earthworms: support for exploring strategies to limit further spread
Authors: HALE CINDY M. 
Published: February 2008

AbstractAs potent ecosystem engineers, non‐native earthworms are altering the fundamental structure and function of previously earthworm‐free cold‐temperate hardwood forests in North America. Discarded earthworms used for fishing bait has been presumed to be an important vector for the continued spread of non‐native earthworms because epicentres of invasion often include boat landings, lakeshores and roads. However, controversy has remained about the overall importance of human‐mediated spread vs. natural expansion of established earthworm populations. In this issue of Molecular Ecology, Cameron et al. explore the continued role of humans in dispersing non‐native earthworms.
Female dispersal and male kinship–based association in southern hairy‐nosed wombats (Lasiorhinus latifrons)
Authors: WALKER FAITH M. , TAYLOR ANDREA C. , SUNNUCKS PAUL 
Published: February 2008

AbstractGeneralizations about sociobiology require investigations of species with diverse ecological roles and phylogenetic affiliations. The southern hairy‐nosed wombat (Lasiorhinus latifrons) is valuable here, in that it is a marsupial of semi‐arid habitat, and one of the largest burrowing herbivores (commonly attaining 26 kg). Its sociobiology is poorly understood because the species is nocturnal, shy, and difficult to observe or capture nondisruptively. To investigate aspects of the species’ sociobiology in continuous habitat, we applied high‐intensity, temporally replicated, noninvasive sampling and genotyping of hairs to identify individuals and their sex. Spatial relatedness (kinship) structure was estimated, and related to patterns of burrow‐use. To understand the association of kinship with burrow/warren‐sharing and preferential colocation between wombats, > 100 genetically ‘tagged’ individuals at Brookfield Conservation Park (Murraylands, South Australia) were ‘tracked’ through multiple seasons between 1999 and 2001. Dispersal was female‐biased, and may be performed by females after breeding. Conversely, males were philopatric. Male kin relationships were characterized by preferential burrow‐ and warren‐sharing among closely related males, often in associations lasting for years. In contrast, females under‐associated with their close female relatives and did not form matrilineal groupings with potential for favourable kin interactions. This fundamental departure from the predominant mammalian pattern raises questions about the origins and maintenance of the system, which is now known from all three species of wombat. The present study provides starting points to address those questions by adding to our knowledge of longitudinal spatiotemporal associations and habitat use of a marsupial with the unusual system of female‐biased dispersal, and by outlining robust methodologies.
Abscisic acid deficiency in the tomato mutant high‐pigment 3 leading to increased plastid number and higher fruit lycopene content
Authors: Galpaz Navot , Wang Qiang , Menda Naama , Zamir Dani , Hirschberg Joseph 
Published: February 2008

SummaryCarotenoids are present in most tissues of higher plants where they play a variety of essential roles. To study the regulation of carotenoid biosynthesis, we have isolated novel mutations in tomato (Solanum lycopersicum) with altered pigmentation of fruit or flowers. Here we describe the isolation and analysis of a tomato mutant, high‐pigment 3 (hp3), that accumulates 30% more carotenoids in the mature fruit. Higher concentrations of carotenoids and chlorophyll were also measured in leaves and the pericarp of green fruit. The mutation in hp3 had occurred in the gene for zeaxanthin epoxidase (Zep), which converts zeaxanthin to violaxanthin. Consequently, leaves of the mutant lack violaxanthin and neoxanthin, and flowers contain only minute quantities of these xanthophylls. The concentration in the hp3 mutant of abscisic acid (ABA), which is derived from xanthophylls, is 75% lower than the normal level, making hp3 an ABA‐deficient mutant. The plastid compartment size in fruit cells is at least twofold larger in hp3 plants compared with the wild‐type. The transcript level in the green fruit of FtsZ, which encodes a tubulin‐like protein involved in plastid division, is 60% higher in hp3 than in the wild‐type, suggesting that increased plastid division is responsible for this phenomenon. Elevated fruit pigmentation and plastid compartment size were also observed in the ABA‐deficient mutants flacca and sitiens. Taken together, these results suggest that ABA deficiency in the tomato mutant hp3 leads to enlargement of the plastid compartment size, probably by increasing plastid division, thus enabling greater biosynthesis and a higher storage capacity of the pigments.
The pyruvate, orthophosphate dikinase regulatory proteins of Arabidopsis possess a novel, unprecedented Ser/Thr protein kinase primary structure
Authors: Chastain Chris J. , Xu Wenxin , Parsley Kate , Sarath Gautam , Hibberd Julian M. , Chollet Raymond 
Published: February 2008

SummaryPyruvate, orthophosphate dikinase (PPDK) is a ubiquitous, low‐abundance metabolic enzyme of undetermined function in C3 plants. Its activity in C3 chloroplasts is light‐regulated via reversible phosphorylation of an active‐site Thr residue by the PPDK regulatory protein (RP), a most unusual bifunctional protein kinase (PK)/protein phosphatase (PP). In this paper we document the molecular cloning and functional analysis of the two unique C3 RPs in Arabidopsis thaliana. The first of these, AtRP1, encodes a typical chloroplast‐targeted, bifunctional C4‐like RP. The second RP gene, AtRP2, encodes a monofunctional polypeptide that possesses in vitro RP‐like PK activity but lacks PP activity, and is localized in the cytosol. Notably, the deduced primary structures of these two highly homologous polypeptides are devoid of any canonical subdomain structure that unifies all known eukaryotic and prokaryotic Ser/Thr PKs into one of three superfamilies, despite the direct demonstration that AtRP1 is functionally a member of this group. Instead, these C3 RPs and the related C4 plant homologues encode a conserved, centrally positioned, approximately 260‐residue sequence currently described as the ‘domain of unknown function 299′ (DUF 299). We propose that vascular plant RPs form a unique protein kinase family now designated as the DUF 299 gene family.