bluuebunny/crossref_metadata_2025 huggingface dataset:
Free methionine-(
R
)-sulfoxide reductase from
Escherichia coli
reveals a new GAF domain function
Authors: Lin Zhidong , Johnson Lynnette C. , Weissbach Herbert , Brot Nathan , Lively Mark O. , Lowther W. Todd
Published: May 2007

The reduction of methionine sulfoxide (MetO) is mediated by methionine sulfoxide reductases (Msr). The MsrA and MsrB families can reduce free MetO and MetO within a peptide or protein context. This process is stereospecific with the
S
- and
R
-forms of MetO repaired by MsrA and MsrB, respectively. Cell extracts from an MsrA
−
B
−
knockout of
Escherichia coli
have several remaining Msr activities. This study has identified an enzyme specific for the free form of Met-(
R
)-O, fRMsr, through proteomic analysis. The recombinant enzyme exhibits the same substrate specificity and is as active as MsrA family members.
E. coli
fRMsr is, however, 100- to 1,000-fold more active than non-selenocysteine-containing MsrB enzymes for free Met-(
R
)-O. The crystal structure of
E. coli
fRMsr was previously determined, but no known function was assigned. Thus, the function of this protein has now been determined. The structural similarity of the
E. coli
and yeast proteins suggests that most fRMsrs use three cysteine residues for catalysis and the formation of a disulfide bond to enclose a small active site cavity. This latter feature is most likely a key determinant of substrate specificity. Moreover,
E. coli
fRMsr is the first GAF domain family member to show enzymatic activity. Other GAF domain proteins substitute the Cys residues and others to specifically bind cyclic nucleotides, chromophores, and many other ligands for signal potentiation. Therefore, Met-(
R
)-O may represent a signaling molecule in response to oxidative stress and nutrients via the TOR pathway in some organisms.
Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR
Authors: Lytle J. Robin , Yario Therese A. , Steitz Joan A.
Published: May 2007

In animals, microRNAs (miRNAs) bind to the 3′ UTRs of their target mRNAs and interfere with translation, although the exact mechanism of inhibition of protein synthesis remains unclear. Functional miRNA-binding sites in the coding regions or 5′ UTRs of endogenous mRNAs have not been identified. We studied the effect of introducing miRNA target sites into the 5′ UTR of luciferase reporter mRNAs containing internal ribosome entry sites (IRESs), so that potential steric hindrance by a microribonucleoprotein complex would not interfere with the initiation of translation. In human HeLa cells, which express endogenous let-7a miRNA, the translational efficiency of these IRES-containing reporters with 5′ let-7 complementary sites from the
Caenorhabditis elegans
lin-41 3′ UTR was repressed. Similarly, the IRES-containing reporters were translationally repressed when human Ago2 was tethered to either the 5′ or 3′ UTR. Interestingly, the method of DNA transfection affected our ability to observe miRNA-mediated repression. Our results suggest that association with any position on a target mRNA is mechanistically sufficient for a microribonucleoprotein to exert repression of translation at some step downstream of initiation.
Identifying pattern-defined regulatory islands in mammalian genomes
Authors: Cheung Tom H. , Barthel Kristen K. B. , Kwan Yin Lam , Liu Xuedong
Published: May 2007

Identifying cis-regulatory regions in mammalian genomes is a key challenge toward understanding transcriptional regulation. However, identification and functional characterization of those regulatory elements governing differential gene expression has been hampered by the limited understanding of their organization and locations in genomes. We hypothesized that genes that are conserved across species will also display conservation at the level of their transcriptional regulation and that this will be reflected in the organization of cis-elements mediating this regulation. Using a computational approach, clusters of transcription factor binding sites that are absolutely conserved in order and in spacing across human, rat, and mouse genomes were identified. We term these regions pattern-defined regulatory islands (PRIs). We discovered that these sequences are frequently active sites of transcriptional regulation. These PRIs occur in ≈1.1% of the half-billion base pairs covered in the search and are located mainly in noncoding regions of the genome. We show that the premise of PRIs can be used to identify previously known and novel cis-regulatory regions controlling genes regulated by myogenic differentiation. Thus, PRIs may represent a fundamental property of the architecture of cis-regulatory elements in mammalian genomes, and this feature can be exploited to pinpoint critical transcriptional regulatory elements governing cell type-specific gene expression.
Patient, clinician, and general practice factors in long-term certified sickness
Authors: Shiels Christopher , Gabbay Mark B.
Published: May 2007

Aims: To investigate the association of patient, clinician, and general practice factors with long-term certified sickness absence. Methods: Analysis of a sickness certification database constructed via the use of carbonized sick notes by clinicians at nine general practices in the north-west of England. A total of 3,385 patient sickness episodes certified by 44 general practitioners (GPs) were included in the analysis. Three logistic regression models were constructed in order to estimate independent effects of the patient, GP, and the general practice on risk of long-term (>28 weeks) incapacity. Results: The logistic regression models explained a maximum of 27% of the variation in long-term certified sickness. The diagnostic reason for the sickness episode explained over 18% of variance, while clinician and general practice effects explained only 3.4% and 2.3% respectively. In all models, older patient age and an episode within the mild mental disorder (MMD) diagnostic category significantly increased the risk of long-term work incapacity. Conclusions: The study results imply that, rather than basing `return to work' interventions on identification of individual patient/claimant characteristics or on GP training initiatives, it may be more productive to focus upon a more diagnosis-based approach within primary care itself. Interventions aiming to reduce mild mental disorder-related work incapacity should be given priority.
Humour, beauty, and culture as personal health resources: Experiences of elderly Swedish women
Authors: Forssén Annika S.K.
Published: May 2007

Aim: This paper explores how a group of elderly women used humour, beauty, and cultural activities to maintain physical and mental well-being. Methods: The paper reports on one aspect of a qualitative study on women's work and health in a lifetime perspective. Interviews with 20 strategically selected Swedish women, aged 63 to 83 years, were audiotaped and analysed according to a phenomenological approach. Results: During the interview process, the researchers became increasingly aware that the women had clear ideas about what enabled them to feel well and healthy — even when actually quite diseased. Creating and enjoying humour, beauty, and culture formed part of such strategies. Joking with workmates made hard, low-status jobs easier, helped them endure pain, and helped balance marital difficulties. Creating a nice and comfortable home gave pleasure and a little luxury in a life filled with necessities. Making articles for everyday use more beautiful was regarded as worthwhile, because it gave delight to them and their families. Gains from cultural activities were social, aesthetic, and existential — the latter through a feeling of self-recognition and being heard. Conclusions: Humour, beauty, and culture formed a greater part of these women's survival strategies than expected. Making everyday life more aesthetic is an undervalued aspect of women's health-creating work in the family. Through their lifelong experience as carers and homemakers, elderly women possess special knowledge regarding what may promote health, a knowledge that should be tapped. When supplying elderly women with social care, their needs for humour, beauty, and culture should be respected.
Mortality in the Sami population of North Norway, 1970—98
Authors: Tynes Tore , Haldorsen Tor
Published: May 2007

Aims: The pattern of mortality among many groups of indigenous people has been shown to be disadvantageous in comparison with the general population. Knowledge regarding causes of death among the Sami population in the northern part of Norway is limited. The Sami constitute an ethnic minority whose lifestyle diverges from that of the rest of the population. Methods: A cohort of 19,801 persons of Sami origin was followed up to evaluate specific causes of mortality during the period 1970—98. Standardized mortality rates (SMR) were calculated using the rural population of the three Norwegian counties included in the study as a reference population. Results: Among Sami, 5,955 total deaths were observed, as opposed to 5,537 expected (SMR=1.08). For both Sami women and men a significantly higher SMR for cerebrovascular diseases was found, which was more pronounced for women. For Sami men, an excess SMR for violent death was observed (SMR 1.32, 95% confidence interval (CI) 1.20—1.46); this was highest among Sami men living in a reindeer-breeding family. For both genders, mortality from all malignant neoplasms combined was lower than in the reference population. SMRs were 0.86 (95% CI 0.79—0.94) and 0.89 (95% CI 0.80—0.99) for men and women, respectively. Low SMRs were also observed for chronic liver diseases, 0.18 (95% CI 0.02—0.63) and 0.12 (95% CI 0.00—0.68) for Sami men and women, respectively. To be a member of a reindeer breeding household appeared to offer protection from mortality caused by circulatory system diseases in men, especially mortality from ischaemic heart disease. Conclusions: The total mortality in the North Norway Sami population, an ethnic minority in Norway, was slightly higher when compared with a regional reference population. The differences observed when evaluating mortality by diagnosis might be due to lifestyle, diet, psychosocial, and/or genetic factors.
DNA damage-induced cellular senescence is sufficient to suppress tumorigenesis: a mouse model
Authors: Van Nguyen Thang , Puebla-Osorio Nahum , Pang Hui , Dujka Melanie E. , Zhu Chengming
Published: May 2007

Tumor suppressor p53-dependent apoptosis is critical in suppressing tumorigenesis. Previously, we reported that DNA double-strand breaks (DSBs) at the V(D)J recombination loci induced genomic instability in the developing lymphocytes of nonhomologous end-joining (NHEJ)–deficient, p53-deficient mice, which led to rapid lymphomagenesis. To test the ability of p53-dependent cell cycle arrest to suppress tumorigenesis in the absence of apoptosis in vivo, we crossbred NHEJ-deficient mice into a mutant p53R172P background; these mice have defects in apoptosis induction, but not cell cycle arrest. These double-mutant mice survived longer than NHEJ/p53 double-null mice and, remarkably, were completely tumor free. We detected accumulation of aberrant V(D)J recombination–related DSBs at the T cell receptor (TCR) locus, and high expression levels of both mutant p53 and cell cycle checkpoint protein p21, but not the apoptotic protein p53-upregulated modulator of apoptosis. In addition, a substantial number of senescent cells were observed among both thymocytes and bone marrow cells. Cytogenetic studies revealed euploidy and limited chromosomal breaks in these lymphoid cells. The results indicate that precursor lymphocytes, which normally possess a high proliferation potential, are able to withdraw from the cell cycle and undergo senescence in response to the persistence of DSBs in a p53–p21–dependent pathway; this is sufficient to inhibit oncogenic chromosomal abnormality and suppress tumorigenesis.
Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting
Authors: Wirzenius Maria , Tammela Tuomas , Uutela Marko , He Yulong , Odorisio Teresa , Zambruno Giovanna , Nagy Janice A. , Dvorak Harold F. , Ylä-Herttuala Seppo , Shibuya Masabumi , Alitalo Kari
Published: May 2007

Lymphatic vessel growth, or lymphangiogenesis, is regulated by vascular endothelial growth factor-C (VEGF-C) and -D via VEGF receptor 3 (VEGFR-3). Recent studies suggest that VEGF, which does not bind to VEGFR-3, can also induce lymphangiogenesis through unknown mechanisms. To dissect the receptor pathway that triggers VEGFR-3–independent lymphangiogenesis, we used both transgenic and adenoviral overexpression of placenta growth factor (PlGF) and VEGF-E, which are specific activators of VEGFR-1 and -2, respectively. Unlike PlGF, VEGF-E induced circumferential lymphatic vessel hyperplasia, but essentially no new vessel sprouting, when transduced into mouse skin via adenoviral vectors. This effect was not inhibited by blocking VEGF-C and -D. Postnatal lymphatic hyperplasia, without increased density of lymphatic vessels, was also detected in transgenic mice expressing VEGF-E in the skin, but not in mice expressing PlGF. Surprisingly, VEGF-E induced lymphatic hyperplasia postnatally, and it did not rescue the loss of lymphatic vessels in transgenic embryos where VEGF-C and VEGF-D were blocked. Our data suggests that VEGFR-2 signals promote lymphatic vessel enlargement, but unlike in the blood vessels, are not involved in vessel sprouting to generate new lymphatic vessels in vivo.
An Evaluation of the Additive Effect of Natural Herbal Medicine on SARS or SARS‐Like Infectious Diseases in 2003: A Randomized, Double‐Blind, and Controlled Pilot Study
Authors: Hsu Chung-Hua , Hwang Kung-Chang , Chao Chung-Liang , Chang Steve G. N. , Ho Mei-Shang , Lin Jaung-Geng , Chang Hen-Hong , Kao Shung-Te , Chen Yi-Ming , Chou Pesus
Published: May 2007

Natural herbal medicine (NHM) has been used to control infectious diseases for thousands of years. In view of the possible beneficial effect of NHM on SARS, we conducted this study to examine whether NHM is of any benefit as a supplementary treatment of SARS or SARS‐like infectious disease. This was a randomized, double‐blind, placebo‐controlled trial. Twenty‐eight patients fulfilled the WHO inclusion criteria and our exclusion criteria. All enrolled patients received routine western‐medicine treatment. Patients were randomly allocated to one of the three supplementary treatment groups: NHM A (Group A, n = 9) NHM B (Group B, n = 9) or placebo (Group C, n = 10). Chest X‐ray was done every 1 or 2 days for every patient. Reading radiologists use a standard 0–3 scoring system (0: no infiltration; 1: focal haziness or even small patchy lesion; 2: ground glass picture; 3: lobar consolidation) according to the severity of infiltration in each lung field (three lung fields in both right and left lungs). The main outcome measurements were the improving chest radiographic scores (IRS) and the duration (days) till improvement (DI). One patient from the placebo group passed away. Patients from NHM A took less days before showing improvement (6.7 ± 1.8) compared with placebo group (11.2 ± 4.9), which showed statistical significance (P = 0.04). The cases were too few to be conclusive, the initial observations seem to indicate NHM appears to be safe in non‐criticallly ill patients and clinical trials are feasible in the setting of pandemic outbreaks.
Piercing the Corporate Veil: Cape Industries and Multinational Corporate Liability for a Toxic Hazard, 1950–2004
Authors: Tweedale Geoffrey , Flynn Laurie
Published: May 2007

The ‘corporate veil’ refers to the separation of legal identity between parent firms and their subsidiaries, which gives the parent protection against the liabilities of its subsidiaries. Fearing that such liability protection would facilitate illicit activity, early twentieth century courts, especially in America, would sometimes ‘pierce’ the corporate veil. This article explores Adams v. Cape (1990), in which American plaintiffs attempted to persuade the English courts to lift the corporate veil and impose liability for industrial disease on Cape Industries, a leading U.K. asbestos manufacturer. This landmark case shows how corporate strategy can be closely intertwined with international corporate law and occupational health and safety issues. It also highlights how limited liability law and separate legal personality can result in significant injustice to claimants against multinational enterprises.
How did the Invisible Hand Handle Industrial Waste? By-product Development before the Modern Environmental Era
Authors: Desrochers Pierre
Published: May 2007

A growing number of historians have turned their attention to the past behavior of industrialists toward their waste. Many have argued that the price system and competition typically fostered a short-term outlook that rewarded pollution rather than encouraging “loop-closing,” a modern term that refers to the linkages between different industries in which the residual of one becomes the input of another. Others have identified precedents in this respect that are credited to Progressive Era reformers. Building on evidence that has, by and large, escaped the attention of the present generation of historical writers, this essay challenges both views by arguing that market institutions, which included both profit motive and property rights, actually resulted in the usage of industrial by-products. Although past industrial activities did create significant pollution problems, perhaps our ancestors should be given more credit than they generally are for the creativity and resourcefulness they displayed in profitably solving numerous environmental problems.
Quantitative Analysis of Efficient Endogenous Gene Silencing in Nicotiana benthamiana Plants Using Tomato bushy stunt virus Vectors That Retain the Capsid Protein Gene
Authors: Pignatta Daniela , Kumar Pavan , Turina Massimo , Dandekar Abhaya , Falk Bryce W.
Published: May 2007

Tomato bushy stunt virus (TBSV) coat protein (CP) replacement vectors have been used previously to silence transgenes (e.g., the green fluorescent protein gene) but have not been effective for silencing endogenous plant genes. New TBSV vectors which retained the CP gene were developed by engineering an XhoI restriction site in three positions (3f, CEB, and CEA) of the pTBSV-100 infectious clone. Magnesium chelatase (ChlH) and phytoene desaturase (PDS) were chosen as targets for endogenous gene silencing. Initial experiments using CP replacement vectors with a 230-bp sense or antisense ChlH insert gave a silencing phenotype prominent only in the first new leaves above those inoculated. No silencing phenotype was apparent beyond these leaves whereas, for PDS, no silencing phenotype was observed. When plants were inoculated with the XhoI insert vectors containing ChlH and PDS sequences, plants showed a silencing phenotype extensively throughout the challenged plant, indicating an improved ability for virus movement and silencing in Nicotiana benthamiana host plants. Silencing efficiencies were quantified using real-time reverse-transcription polymerase chain reaction, indicating specific silencing effects of each individual silencing vector. Only one recombinant vector (pPD-3f5), where the XhoI insert was at the 3′ end of the CP gene, failed to give effective silencing. Here, we show that our new CP-retaining TBSV vectors (CEA-CEB) form typical TBSV virions, retain silencing inserts of variable lengths (110 to 260 nucleotides), and can systemically silence endogenous genes in N. benthamiana.
Tryptophan-Dependent Production of Indole-3-Acetic Acid (IAA) Affects Level of Plant Growth Promotion by Bacillus amyloliquefaciens FZB42
Authors: Idris ElSorra E. , Iglesias Domingo J. , Talon Manuel , Borriss Rainer
Published: May 2007

Phytohormone-like acting compounds previously have been suggested to be involved in the phytostimulatory action exerted by the plant-beneficial rhizobacterium Bacillus amyloliquefaciens FZB42. Analyses by high-performance liquid chromatography and gas chromatography-mass spectrometry performed with culture filtrates of FZB42 demonstrated the presence of indole-3-acetic acid (IAA), corroborating it as one of the pivotal plant-growth-promoting substances produced by this bacterium. In the presence of 5 mM tryptophan, a fivefold increase in IAA secretion was registered. In addition, in the trp auxotrophic strains E101 (ΔtrpBA) and E102 (ΔtrpED), and in two other strains bearing knockout mutations in genes probably involved in IAA metabolism, E103 (ΔysnE, putative IAA transacetylase) and E105 (ΔyhcX, putative nitrilase), the concentration of IAA in the culture filtrates was diminished. Three of these mutant strains were less efficient in promoting plant growth, indicating that the Trp-dependent synthesis of auxins and plant growth promotion are functionally related in B. amyloliquefaciens.
Complementation ofUstilago maydisMAPK Mutants by a Wheat Leaf Rust,Puccinia triticinaHomolog: Potential for Functional Analyses of Rust Genes
Authors: Hu Guanggan , Kamp Andrena , Linning Rob , Naik Suresh , Bakkeren Guus
Published: May 2007

From a large expressed sequence tag (EST) database representing several developmental stages of Puccinia triticina, we discovered a mitogen-activated protein kinase (MAPK) with homology to kinases with known pathogenic functions in other fungi. This PtMAPK1 is similar to the Ustilago maydis MAPK, Ubc3/Kpp2, but has a longer N-terminal extension of 43 amino acids (aa) with identities to U. maydis Kpp6, a homolog of Ubc3/Kpp2 with a 170-aa N-terminal extension. Ubc3/Kpp2 is involved in mating and subsequent pathogenic development, whereas Kpp6 functions during invasive growth in corn tissue. PtMAPK1, expressed from a Ustilago sp.-specific promoter, was able to complement a ubc3/kpp2 deletion mutant and restore mating. It also substantially increased virulence on corn, measured as tumor formation, of a kpp6 deletion mutant. Moreover, this construct restored to near-full pathogenicity a ubc3/kpp2 kpp6 nonpathogenic double deletion mutant. Complementation of the ubc3/kpp2 mutant with the complete PtMAPK gene and verification of expression by reverse-transcription polymerase chain reaction indicated that the rust promoter is recognized in U. maydis. Phylogenetically, these basidiomycete plant pathogens are related, which was reflected in comparison of P. triticina ESTs to U. maydis gene sequences. The U. maydis heterologous expression system allows functional analysis of rust genes, currently frustrated by the lack of efficient transformation and selection procedures.
Phosphorylation of the Termini of Cauliflower mosaic virus Precapsid Protein Is Important for Productive Infection
Authors: Champagne Julie , Laliberté-Gagné Marie-Eve , Leclerc Denis
Published: May 2007

Cauliflower mosaic virus (CaMV) coat protein precursor (pre-CP) has 489 amino acids (p57) and is processed by the viral proteinase into three major forms: p44, p39, and p37. The N- and C-terminal extensions of pre-CP are released during maturation by the virus-encoded proteinase. We showed that these extensions are phosphorylated at several sites by host casein kinase II (CKII). We have identified the phosphorylated amino acids using an in vitro phosphorylation assay and tested the effect of mutation of these sites on viral infectivity. Mutation of serines S66, S68, and S72 to alanine in the N-terminal extension abolished phosphorylation of the protein in vitro. Also, mutation of all S and T residues in the C-terminus (450 to 489) made this region insensitive to CKII. Amino acid substitutions also were introduced into a full-length infectious clone of CaMV. Mutated forms of the virus with S66, S68, and S72 substituted with A or D showed a delay in symptom development and affected the infectivity of the virus. However, a mutant with an A substitution of all the S and T residues of the C-terminal extension of CP was not infectious. These results suggest that phosphorylation of the N- and C-termini of CaMV pre-CP plays an important role in the initiation of viral infection.
Insect Elicitors and Exposure to Green Leafy Volatiles Differentially Upregulate Major Octadecanoids and Transcripts of 12-Oxo Phytodienoic Acid Reductases in Zea mays
Authors: Engelberth Jürgen , Seidl-Adams Irmgard , Schultz Jack C. , Tumlinson James H.
Published: May 2007

The induction of jasmonic acid (JA) is one of the major signaling events in plants in response to insect herbivore damage and leads to the activation of direct and indirect defensive measures. Green leafy volatiles, which constitute a major portion of volatile organic compounds, often are released in response to insect herbivore attack and have been shown to significantly activate JA production in exposed corn (Zea mays) seedlings, thereby priming these plants specifically against subsequent herbivore attack. To explore the factors determining the specificity of the octadecanoid signaling pathway in corn, we analyzed qualitative and quantitative changes in major octadecanoids. The time course and the amount of induced JA and 12-oxophytodienoic acid levels in corn seedlings were strikingly different after wounding, application of caterpillar regurgitant, or treatment with cis-3-hexenyl acetate (Z-3-6:AC). Exposure to Z-3-6:AC induced accumulation of transcripts encoded by three putative 12-oxophytodienoate10,11-re-ductase genes (ZmOPR1/2, ZmOPR5, and ZmOPR8). Although changes in ZmOPR5 RNAs were detected only after exposure to Z-3-6:AC, ZmOPR1/2 RNAs and ZmOPR8 RNAs also were abundant after treatment with crude regurgitant elicitor or mechanical damage. The physiological implications of these findings in the context of plant-insect interactions are discussed.
Characterization of Stress-ResponsiveCIPKGenes in Rice for Stress Tolerance Improvement
Authors: Xiang Yong , Huang Yuemin , Xiong Lizhong
Published: May 2007

Plants respond to adverse environments by initiating a series of signaling processes that often involves diverse protein kinases, including calcineurin B-like protein-interacting protein kinases (CIPKs). In this study, putative CIPK genes (OsCIPK01–OsCIPK30) in the rice (Oryza sativa) genome were surveyed for their transcriptional responses to various abiotic stresses. The results showed that 20 OsCIPK genes were differentially induced by at least one of the stresses, including drought, salinity, cold, polyethylene glycol, and abscisic acid treatment. Most of the genes induced by drought or salt stress were also induced by abscisic acid treatment but not by cold. A few CIPK genes containing none of the reported stress-responsive cis-elements in their promoter regions were also induced by multiple stresses. To prove that some of these stress-responsive OsCIPK genes are potentially useful for stress-tolerance improvement, three CIPK genes (OsCIPK03, OsCIPK12, and OsCIPK15) were overexpressed in japonica rice ‘Zhonghua 11’. Transgenic plants overexpressing the transgenes OsCIPK03, OsCIPK12, and OsCIPK15 showed significantly improved tolerance to cold, drought, and salt stress, respectively. Under cold and drought stresses, OsCIPK03- and OsCIPK12-overexpressing transgenic plants accumulated significantly higher contents of proline and soluble sugars than the wild type. Putative proline synthetase and transporter genes had significantly higher expression level in the transgenic plants than in the wild type. The differentially induced expression of OsCIPK genes by different stresses and the examples of improved stress tolerance of the OsCIPK transgenic rice suggest that rice CIPK genes have diverse roles in different stress responses and some of them may possess potential usefulness in stress-tolerance improvement of rice.
Structure and Function of a Mitochondrial Late Embryogenesis Abundant Protein Are Revealed by Desiccation
Authors: Tolleter Dimitri , Jaquinod Michel , Mangavel Cécile , Passirani Catherine , Saulnier Patrick , Manon Stephen , Teyssier Emeline , Payet Nicole , Avelange-Macherel Marie-Hélène , Macherel David
Published: May 2007

Few organisms are able to withstand desiccation stress; however, desiccation tolerance is widespread among plant seeds. Survival without water relies on an array of mechanisms, including the accumulation of stress proteins such as the late embryogenesis abundant (LEA) proteins. These hydrophilic proteins are prominent in plant seeds but also found in desiccation-tolerant organisms. In spite of many theories and observations, LEA protein function remains unclear. Here, we show that LEAM, a mitochondrial LEA protein expressed in seeds, is a natively unfolded protein, which reversibly folds into α-helices upon desiccation. Structural modeling revealed an analogy with class A amphipathic helices of apolipoproteins that coat low-density lipoprotein particles in mammals. LEAM appears spontaneously modified by deamidation and oxidation of several residues that contribute to its structural features. LEAM interacts with membranes in the dry state and protects liposomes subjected to drying. The overall results provide strong evidence that LEAM protects the inner mitochondrial membrane during desiccation. According to sequence analyses of several homologous proteins from various desiccation-tolerant organisms, a similar protection mechanism likely acts with other types of cellular membranes.
Analysis of mtDNA sequences shows Japanese native chickens have multiple origins
Authors: Oka T. , Ino Y. , Nomura K. , Kawashima S. , Kuwayama T. , Hanada H. , Amano T. , Takada M. , Takahata N. , Hayashi Y. , Akishinonomiya F.
Published: May 2007

In this study, we analysed the mitochondrial DNA D‐loop region of Japanese native chickens to clarify their phylogenetic relationships, possible maternal origin and routes of introduction into Japan. Seven haplogroups (Types A–G) were identified. Types A–C were observed in Jidori, Shokoku and related breeds. However, Type C was absent in Shokoku, which was introduced from China, while most Indonesian native chickens were included in the Type C haplogroup. Types D–G were observed in Shamo and related breeds. Type E had a close genetic relationship with Chinese native chickens. Our results indicate that some breeds were not introduced into Japan as suggested in conventional literature, based on low nucleotide diversity of certain chicken breeds. Sequences originating from China and Korea could be clearly distinguished from those originating from Southeast Asia. In each group, domestic chickens were divided into the Jidori‐Shokoku and Shamo groups. These results indicate that Chinese and Korean chickens were derived from Southeast Asia. Following the domestication of red junglefowl, a non‐game type chicken was developed, and it spread to China. A game type chicken was developed in each area. Both non‐game and game chickens formed the foundation of Japanese native chickens.
Differential gene expression of aldolase C (ALDOC) and hypoxic adaptation in chickens
Authors: Wang C. F. , Yuan C. Z. , Wang S. H. , Zhang H. , Hu X. X. , Zhang L. , Wu C. , Li N.
Published: May 2007

Two sequence variants of the aldolase C (ALDOC) gene were discovered based on comparison of the sequences from an altiplano chicken breed (Tibetan chicken) and two lowland breeds (White Leghorn and ShouGuang). Gel‐shift results indicated that one of these variants, L25375:c.310‐258G>A, was able to bind hypoxia‐induced factor‐l (HIF1A), therefore, functioning as a hypoxia response element (HRE). The combined activity of the HRE and HIF1A could increase under the influence of a hypoxic stimulus. Hypoxia leads to increased death rates of chicken embryos, while the L25375:c.310‐258G>A described herein is prevalent in healthy embryos grown under hypoxic conditions. Fluorescence quantitative real‐time PCR results revealed that HIF1A upregulated the transcript level of the glycolytic enzyme ALDOC in the brain and skeletal muscle of animals subjected to hypoxia. Thus, a large amount of ATP is produced by increased glycolysis, allowing the organism to meet energy metabolism demands. As such, we believe this sequence variant is an adaptation to external anoxic environment.
Leukaemia‐related gene expression in bone marrow cells from patients with the preleukaemic disorder Shwachman–Diamond syndrome
Authors: Rujkijyanont Piya , Beyene Joseph , Wei Kuiru , Khan Fahad , Dror Yigal
Published: May 2007

Shwachman–Diamond syndrome (SDS) is an inherited bone marrow failure disorder with cytopenia and a high propensity for myelodysplastic syndrome (MDS) and leukaemia, particularly acute myeloid leukaemia. The mechanism of leukaemogenesis in SDS is unknown. In accordance to the multi‐hit theory of carcinogenesis, it is likely that several molecular and cellular hits occur before MDS/leukaemia become apparent. This study used oligonucleotide microarray to identify gene expression patterns, which were shown to be associated with leukaemogenesis, in marrow mononuclear cells of nine SDS patients without overt transformation compared to healthy controls. Among 154 known leukaemia‐related genes, several oncogenes were found to be upregulated, including LARG, TAL1 and MLL, and of several tumour suppressor genes were downregulated, including DLEU1, RUNX1, FANCD2 and DKC1. Real time polymerase chain reaction confirmed statistically higher expression of LARG and TAL1 in SDS marrows. We conclude that SDS marrow mononuclear cells exhibit abnormal gene expression patterns, which might result in continuous stimulation favouring evolution or progression of malignant clones. Additional molecular and cytogenetic events are probably necessary for the malignant process to be irreversible and complete.
Advances in the understanding of susceptibility to treatment‐related acute myeloid leukaemia
Authors: Seedhouse Claire , Russell Nigel
Published: May 2007

Treatment‐related acute myeloid leukaemia (t‐AML) is a devastating complication following exposure to the cytotoxic and genotoxic agents used to treat a primary malignancy. Whilst the incidence of t‐AML is rising, it still only occurs in a minority of patients who have received chemotherapy and/or radiotherapy treatment and hence it is important to identify factors that may confer susceptibility to the development of the condition. This paper reviews the literature and discusses the advances and limitations in our understanding of susceptibility factors to t‐AML. In particular, it concentrates upon genetic polymorphisms in detoxification genes and in genes belonging to the major DNA repair pathways. This review also considers more novel susceptibility factors, such as those proposed to determine stem cell number. Increased understanding of t‐AML susceptibility may enable steps to be taken to prevent its development and increase the effectiveness of treatment of the disease.
High serum levels of B‐lymphocyte stimulator are associated with clinical–pathological features and outcome in classical Hodgkin lymphoma
Authors: Tecchio C. , Nadali G. , Scapini P. , Bonetto C. , Visco C. , Tamassia N. , Vassilakopoulos T. P. , Pangalis G. A. , Calzetti F. , Nardelli B. , Roschke V. , Gottardi M. , Zampieri F. , Gherlinzoni F. , Facchetti F. , Pizzolo G. , Cassatella M. A.
Published: May 2007

B‐lymphocyte stimulator (BLyS) acts as survival factor for B lymphocytes. As Hodgkin and Reed‐Sternberg (HRS) cells express receptors through which BLyS promotes their growth and chemotherapy resistance, we investgated whether this molecule was increased in sera from patients with classical Hodgkin lymphoma (cHL) and whether it correlates with clinical‐pathological features and outcomes. Enzyme‐linked immunosorbent assay was used to measure soluble BLyS (sBLyS) in sera from 87 patients and 33 donors; higher levels were detected in patients (mean ± standard error 4493·9 ± 264·9 pg/ml vs. 2687·0 ± 200·9 pg/ml; P < 0·0001). Levels above the median value (4242·0 pg/ml) were associated with age ≥45 years (P = 0·042), advanced stages of disease (P = 0·005), systemic symptoms (P = 0·014) and extranodal involvement (P = 0·009). Five‐year failure‐free survival (FFS) of patients with sBLyS below or equal to median levels was 88·6% as compared to 65·1% of those with levels above the median (P = 0·009). Statistical analyses confirmed the prognostic significance of sBLyS (P = 0·046). When patients were analysed according to variables associated with high levels, sBLyS showed an independent predictive power in terms of FFS. Our findings support the involvement of BLyS in cHL pathogenesis. The association between high serum levels and an inferior FFS indicates that sBLyS is a possible prognostic predictor with a potential significance as a therapeutic target.
Responses of larval dragonflies to conspecific and heterospecific predator cues
Authors: FERRIS GAVIN , RUDOLF VOLKER H. W.
Published: May 2007

Abstract 1. In cannibalistic populations, smaller individuals are subject to predation by larger conspecifics, and small individuals commonly alter their behaviour in response to cannibals. Little is known, however, about the underlying cues that trigger such responses and how the behavioural responses to conspecific cannibals differ from heterospecific predators.

2. This study tests which cues are used for the detection of conspecific predators in the larva of the dragonfly Plathemis lydia and how the behavioural response to cannibals differed from the response to heterospecific predators.

3. Individuals were exposed to chemical cues, visual cues, and a combination of both cues from conspecifics as well as no predator and heterospecific predator controls during which their activity and feeding rates were observed.

4. Individuals increased their activity, spatial movement and feeding behaviour in response to either visual or chemical cues from conspecific predators, which was opposite to responses displayed with cues from heterospecific predators. Interestingly, the responses to visual and chemical cues from conspecifics combined were weaker than to either cue in isolation and similar to the no cue control.

5. The results clearly indicate that individuals are able to use chemical and visual cues to detect even very subtle differences in phenotype of conspecific predators.

6. The opposite response in behaviour when exposed to conspecific cannibals vs. heterospecific predators suggests that the presence of cannibals will increase the mortality risk of small individuals due to heterospecific predation. This risk‐enhancement is likely to have important consequences for the dynamics of predator–prey interactions.
Achieving high sexual size dimorphism in insects: females add instars
Authors: ESPERK TOOMAS , TAMMARU TOOMAS , NYLIN SÖREN , TEDER TIIT
Published: May 2007

Abstract 1. In arthropods, the evolution of sexual size dimorphism (SSD) may be constrained by a physiological limit on growth within each particular larval instar. A high SSD could, however, be attained if the larvae of the larger sex pass through a higher number of larval instars.

2. Based on a survey of published case studies, the present review shows that sex‐related difference in the number of instars is a widespread phenomenon among insects. In the great majority of species with a sexually dimorphic instar number, females develop through a higher number of instars than males.

3. Female‐biased sexual dimorphism in final sizes in species with sexually dimorphic instar number was found to considerably exceed a previously estimated median value of SSD for insects in general. This suggests a causal connection between high female‐biased SSD, and additional instars in females. Adding an extra instar to larval development allows an insect to increase its adult size at the expense of prolonged larval development.

4. As in the case of additional instars, SSD is fully formed late in ontogeny, larval growth schedules and imaginal sizes can be optimised independently. No conflict between selective pressures operating in juvenile and adult stages is therefore expected.

5. In most species considered, the number of instars also varied within the sexes. Phenotypic plasticity in instar number may thus be a precondition for a sexual difference in instar number to evolve.
Competition trade‐offs in the organisation of a Mediterranean ant assemblage
Authors: SANTINI GIACOMO , TUCCI LORENZO , OTTONETTI LORENZO , FRIZZI FILIPPO
Published: May 2007

Abstract 1. The organisation of an ant assemblage inhabiting an olive orchard in central Italy was analysed and patterns of dominance among ant species were described in order to assess (i) the relationship between thermal dependency and degree of behavioural dominance, and (ii) the relationship between dominance and discovery ability.

2. Activity patterns of the most abundant species on trees were examined in a sample of 120 trees during spring and summer. The degree of behavioural dominance and the ability of different species to discover new food sources were assessed using tuna baiting on a subset of 80 trees.

3. Different ant species showed contrasting patterns of activity. Some species (such as Lasius lasioides, Camponotus lateralis, and Camponotus piceus) were most active during the warmer part of the day, while others restricted their activity to the cooler hours (Camponotus aethiops and Plagiolepis pygmaea). Some species (such as Crematogaster scutellaris) were active irrespective of the time of day.

4. No clear relationship was observed between temperature of maximal activity and degree of behavioural dominance. There was, however, a positive relationship between behavioural dominance and thermal range of activity. A positive relationship between dominance and ability to find resources, with the most behaviourally dominant and aggressive species being most efficient in finding food items, was also observed.

5. The results support the idea that the temperature–dominance relationship is much more complex in Mediterranean‐type habitats than in other ecosystems. Of particular interest is the positive dominance–discovery relationship. This finding contrasts with previous investigations, which reported a negative relationship between dominance and discovery ability and suggested that this pattern plays a role in promoting the coexistence of species in ant communities.
ADMA correlates with portal pressure in patients with compensated cirrhosis
Authors: Vizzutti F. , Romanelli R. G. , Arena U. , Rega L. , Brogi M. , Calabresi C. , Masini E. , Tarquini R. , Zipoli M. , Boddi V. , Marra F. , Laffi G. , Pinzani M.
Published: May 2007

Background  Chronic liver diseases are frequently complicated by portal hypertension, an important component of which is the increased intrahepatic vascular resistance, in part related to endothelial dysfunction. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is an established mediator and marker of endothelial dysfunction. We therefore investigated the possible implication of ADMA in chronic liver diseases‐induced portal hypertension.

Materials and methods  We studied 39 consecutive patients with compensated hepatitis C virus (HCV) related chronic liver diseases. All patients underwent hepatic venous pressure gradient (HVPG) measurement, and simultaneous blood sampling from the hepatic vein and the pulmonary artery, for ADMA and nitrite/nitrate (NOx) plasma level determinations.

Results  A positive correlation between HVPG and ADMA concentrations in hepatic veins (ADMA‐h) was found (r = 0·77, P < 0·0001). Moreover, a negative correlation between HVPG and NOx concentrations in the hepatic veins (NO‐h) (r = −0·50, P = 0·005), and between ADMA‐h and NO‐h was observed (r = −0·40, P = 0·02). ADMA concentrations in pulmonary artery (ADMA‐p) (0·55 ± 0·13 µmol L−1) were significantly higher than in hepatic veins (0·47 ± 0·09 µmol L−1) (P < 0·0001).

Conclusions  These results suggest that ADMA may play a pathophysiological role in portal hypertension by contributing to the relative intrahepatic NO deficiency typical of endothelial dysfunction.
Tolerization of an established αB‐crystallin‐reactive T‐cell response by intravenous antigen
Authors: Verbeek Richard , Van Der Mark Koen , Wawrousek Eric F. , Plomp Arianne C. , Van Noort Johannes M.
Published: May 2007

Tolerance induction to prevent activation of a naïve T‐cell repertoire has been well documented in rodents and can be readily achieved by intravenous, oral or intranasal administration of antigen in the absence of adjuvants. In autoimmune diseases such as multiple sclerosis (MS) the presence of an established memory/effector T‐cell repertoire against self‐antigens is likely to be more relevant than the potential reactivity of naive T cells. Methods to eliminate such an established T‐cell response are less well understood. In this study, we explored the effectiveness of intravenous soluble antigen to eliminate a pre‐existing T‐cell response against αB‐crystallin, a candidate autoantigen in MS. We used mice that are deficient for the target antigen. This condition allowed for a vigourous T‐cell and antibody response to develop upon immunization, and eliminated all possible endogenous mechanisms of tolerance for αB‐crystallin that are found in normal rodents. When applied 3 weeks after priming with αB‐crystallin, intravenous administration of soluble antigen almost completely abrogated the established T‐cell response in a dose‐dependent manner as evidenced by T‐cell non‐responsiveness in tolerized animals to a re‐challenge with antigen in complete Freund's adjuvant. Evaluating delayed‐type hypersensitivity responses after tolerance induction revealed that the tolerizing effect was achieved within 24 hr. Furthermore, the tolerizing effect was found to be antigen‐specific and long lasting. In contrast, serum antibody levels were markedly increased. Our data clarify that in the absence of any natural form of immune regulation, antigen‐specific memory/effector T cells can be effectively silenced by intravenous antigen.
Measuring individualized nursing care: assessment of reliability and validity of three scales
Authors: Suhonen Riitta , Schmidt Lee A. , Radwin Laurel
Published: May 2007

Title. Measuring individualized nursing care: assessment of reliability and validity of three scales

Aim.  This paper is a report of a study to assess the reliability and convergent validity of three measures of nursing care individualization.

Background.  Individualized care is a key element of nursing care quality, yet little is known about the extent to which it is implemented, its effects, and the factors that help or hinder nurses in giving individualized care. Therefore reliable and valid instruments are needed to measure individualized nursing care.

Method.  A cross‐sectional correlational survey design was used. The purposive sample consisted of 861 patients from six hospitals in Finland (response rate 82%). Data were collected in 2004. The Individualized Care Scale was administered simultaneously with translated versions of the Schmidt's Perceptions of Nursing Care Survey and the Oncology Patients’ Perceptions of the Quality of Nursing Care Scale. Internal consistency reliability and convergent validity were assessed for each scale.

Findings.  Evidence for convergent validity was identified between the Individualized Care Scale (part A/B), the Individualization subscale (r = 0·64 with Part A, r = 0·66 with part B) and the Seeing the Individual Patient subscale (r = 0·68 with part A, r = 0·71 with part B). Cronbach alpha coefficient was 0·97 for the Individualized Care Scale, 0·82 for Seeing the Individual Patient and 0·87 for the Individualization subscale.

Conclusion.  Data provided preliminary evidence for the convergent validity of the individualized care scales, as well as acceptable internal consistency reliability for each scale. These scales represent useful measures for assessing patients’ perceptions of the individualization of nursing care received.