bluuebunny/crossref_metadata_2025 huggingface dataset:
Within- and across-flock genetic relationships for breech flystrike resistance indicator traits
Authors: Brown D. J. , Swan A. A. , Gill J. S.
Published: January 2012

Flystrike is a major cost for the Australian sheep industry. The industry is currently implementing selection strategies for flystrike resistance to reduce the need for breech flystrike prevention. The following indicator traits are used to select for breech flystrike resistance: wool cover, skin wrinkle on the body and breech, scouring (dags) and wool colour. The aims of this study were to estimate genetic correlations between these indicator traits and production traits using the Sheep Genetics database, to distinguish between within- and across-flock genetic relationships, and to quantify responses to selection using indexes that include breech wrinkle as a proxy trait for flystrike resistance. Breech flystrike indicator traits are all heritable; however, there are significant antagonisms between wrinkle score and some production traits, primarily fleece weight and fibre diameter. Thus, simultaneous improvement in both flystrike resistance and production will be most efficient when index selection is used. Our results show that, depending on the level of emphasis placed on breech wrinkle in the index, reductions in breech wrinkle score of 0.4–0.9 units can be achieved over a 10-year period. As across-flock relationships are generally stronger than within-flock relationships, breeders will be able to take advantage of this additional variation, depending on the relative merit of their flocks. Therefore, ram breeders should combine within-flock selection with across-flock selection where possible. Sheep Genetics released early breech wrinkle Australian Sheep Breeding Values in September 2009 to assist Merino breeders in making faster progress towards reducing breech wrinkle by using flock selection.
Integrated parasite management for sheep reduces the effects of gastrointestinal nematodes on the Northern Tablelands of New South Wales
Authors: Kelly G. A. , Kahn L. P. , Walkden-Brown S. W.
Published: January 2012

An experiment was conducted over 2 years on six commercial farms to quantify the costs of gastrointestinal nematode parasitism on grazing Merino ewes on the Northern Tablelands of New South Wales. To determine the effect of worm management practices, three farms implemented integrated parasite management (IPM) strategies and three farms continued to implement regionally typical industry practice (TYP). On each farm, 120 ewes born in 2006 and 120 mature age ewes were selected at shearing in 2007. Of these, 60 in each flock were serially treated with anthelmintics (CAP treatment) to suppress worm populations and the other 60 ewes were managed according to their respective farm management strategies (NOCAP treatment). Among NOCAP ewes, worm egg counts were significantly reduced over both years by IPM compared with TYP despite IPM farms requiring fewer anthelmintic treatments (3.5 vs 4.5 per year). In Year 1, mortality of sheep because of worms (CAP vs NOCAP) was significant on TYP farms (10.5%, P < 0.01) but was not apparent on IPM farms. Throughout the study, NOCAP ewes had significantly lower growth rates (–2.8 ± 0.1 kg/year, P < 0.01), produced less greasy wool (–170 ± 20 g, P < 0.01) and had reduced fibre diameter (–0.28 ± 0.05 μm, P < 0.01) when compared with CAP ewes. These effects were apparent for both TYP and IPM management. The results confirm the significant production loss caused by worms in a northern, summer rainfall region and show that IPM reduces the effect of worms and frequency of anthelmintic treatment compared with typical methods currently used by the industry.
Interplay between mismatch repair and chromatin assembly
Authors: Schöpf Barbara , Bregenhorn Stephanie , Quivy Jean-Pierre , Kadyrov Farid A. , Almouzni Genevieve , Jiricny Josef
Published: January 2012

Single strand nicks and gaps in DNA have been reported to increase the efficiency of nucleosome loading mediated by chromatin assembly factor 1 (CAF-1). However, on mismatch-containing substrates, these strand discontinuities are utilized by the mismatch repair (MMR) system as loading sites for exonuclease 1, at which degradation of the error-containing strand commences. Because packaging of DNA into chromatin might inhibit MMR, we were interested to learn whether chromatin assembly is differentially regulated on heteroduplex and homoduplex substrates. We now show that the presence of a mismatch in a nicked plasmid substrate delays nucleosome loading in human cell extracts. Our data also suggest that, once the mismatch is removed, repair of the single-stranded gap is accompanied by efficient nucleosome loading. We postulated that the balance between MMR and chromatin assembly might be governed by proliferating cell nuclear antigen (PCNA), the processivity factor of replicative DNA polymerases, which is loaded at DNA termini and which interacts with the MSH6 subunit of the mismatch recognition factor MutSα, as well as with CAF-1. We now show that this regulation might be more complex; MutSα and CAF-1 interact not only with PCNA, but also with each other. In vivo this interaction increases during S-phase and may be controlled by the phosphorylation status of the p150 subunit of CAF-1.
Reconciling long-term cultural diversity and short-term collective social behavior
Authors: Valori Luca , Picciolo Francesco , Allansdottir Agnes , Garlaschelli Diego
Published: January 2012

An outstanding open problem is whether collective social phenomena occurring over short timescales can systematically reduce cultural heterogeneity in the long run, and whether offline and online human interactions contribute differently to the process. Theoretical models suggest that short-term collective behavior and long-term cultural diversity are mutually excluding, since they require very different levels of social influence. The latter jointly depends on two factors: the topology of the underlying social network and the overlap between individuals in multidimensional cultural space. However, while the empirical properties of social networks are intensively studied, little is known about the large-scale organization of real societies in cultural space, so that random input specifications are necessarily used in models. Here we use a large dataset to perform a high-dimensional analysis of the scientific beliefs of thousands of Europeans. We find that interopinion correlations determine a nontrivial ultrametric hierarchy of individuals in cultural space. When empirical data are used as inputs in models, ultrametricity has strong and counterintuitive effects. On short timescales, it facilitates a symmetry-breaking phase transition triggering coordinated social behavior. On long timescales, it suppresses cultural convergence by restricting it within disjoint groups. Moreover, ultrametricity implies that these results are surprisingly robust to modifications of the dynamical rules considered. Thus the empirical distribution of individuals in cultural space appears to systematically optimize the coexistence of short-term collective behavior and long-term cultural diversity, which can be realized simultaneously for the same moderate level of mutual influence in a diverse range of online and offline settings.
Phytochrome regulates translation of mRNA in the cytosol
Authors: Paik Inyup , Yang Seungchan , Choi Giltsu
Published: January 2012

An array of photoreceptors including cryptochromes, phototropin, and phytochromes regulates various light responses in plants. Among these photoreceptors, phytochromes perceive red and far-red light by switching between two interconvertible spectral forms (Pr and Pfr). The Pfr form promotes light responses partly by destabilizing negatively acting, phytochrome-interacting basic helix-loop-helix transcription factors (PIFs), thus modulating transcription in the nucleus. The Pfr form is also present in the cytosol. However, the role of phytochromes in the cytosol is not well understood. Here we show that the Pfr form interacts with the cytosolic protein PENTA1 (PNT1) and inhibits the translation of protochlorophyllide reductase (
PORA
) mRNA. PNT1 possesses five C3H-type zinc finger domains and displays similarity to various RNA binding proteins including Tristetraprolin, which regulates stabilities of mRNAs such as TNF-α mRNA in humans. Consistent with its function as an RNA binding protein, PNT1 directly binds to mRNA of a key chlorophyll biosynthetic gene, protochlorophyllide reductase in vivo and inhibits the translation of
PORA
mRNA in the presence of phytochromes. The present results demonstrate that phytochromes transmit light signals to regulate not only transcription in the nucleus through PIFs, but also translation in the cytosol through PNT1.
Lipidomic discovery of deoxysiderophores reveals a revised mycobactin biosynthesis pathway in
Mycobacterium tuberculosis
Authors: Madigan Cressida A. , Cheng Tan-Yun , Layre Emilie , Young David C. , McConnell Matthew J. , Debono C. Anthony , Murry Jeffrey P. , Wei Jun-Rong , Barry Clifton E. , Rodriguez G. Marcela , Matsunaga Isamu , Rubin Eric J. , Moody D. Branch
Published: January 2012

To measure molecular changes underlying pathogen adaptation, we generated a searchable dataset of more than 12,000 mass spectrometry events, corresponding to lipids and small molecules that constitute a lipidome for
Mycobacterium tuberculosis
. Iron is essential for
M. tuberculosis
survival, and the organism imports this metal using mycobactin and carboxymycobactin siderophores. Detection of an unexpected siderophore variant and deletions of genes for iron scavenging has led to a revised mycobactin biosynthesis model. An organism-wide search of the
M. tuberculosis
database for hypothetical compounds predicted by this model led to the discovery of two families of previously unknown lipids, designated monodeoxymycobactins and monodeoxycarboxymycobactins. These molecules suggest a revised biosynthetic model that alters the substrates and order of action of enzymes through the mycobactin biosynthetic pathway. We tested this model genetically by solving
M. tuberculosis
lipidomes after deletion of the iron-dependent regulator (
ideR
), mycobactin synthase B (
mbtB
), or mycobactin synthase G (
mbtG
). These studies show that deoxymycobactins are actively regulated during iron starvation, and also define essential roles of MbtG in converting deoxymycobactins to mycobactin and in promoting
M. tuberculosis
growth. Thus, lipidomics is an efficient discovery tool that informs genetic relationships, leading to a revised general model for the biosynthesis of these virulence-conferring siderophores.
Gut inflammation can boost horizontal gene transfer between pathogenic and commensal
Enterobacteriaceae
Authors: Stecher Bärbel , Denzler Rémy , Maier Lisa , Bernet Florian , Sanders Mandy J. , Pickard Derek J. , Barthel Manja , Westendorf Astrid M. , Krogfelt Karen A. , Walker Alan W. , Ackermann Martin , Dobrindt Ulrich , Thomson Nicholas R. , Hardt Wolf-Dietrich
Published: January 2012

The mammalian gut harbors a dense microbial community interacting in multiple ways, including horizontal gene transfer (HGT). Pangenome analyses established particularly high levels of genetic flux between Gram-negative
Enterobacteriaceae
. However, the mechanisms fostering intraenterobacterial HGT are incompletely understood. Using a mouse colitis model, we found that
Salmonella
-inflicted enteropathy elicits parallel blooms of the pathogen and of resident commensal
Escherichia coli
. These blooms boosted conjugative HGT of the colicin-plasmid p2 from
Salmonella enterica
serovar Typhimurium to
E. coli
. Transconjugation efficiencies of ∼100% in vivo were attributable to high intrinsic p2-transfer rates. Plasmid-encoded fitness benefits contributed little. Under normal conditions, HGT was blocked by the commensal microbiota inhibiting contact-dependent conjugation between
Enterobacteriaceae
. Our data show that pathogen-driven inflammatory responses in the gut can generate transient enterobacterial blooms in which conjugative transfer occurs at unprecedented rates. These blooms may favor reassortment of plasmid-encoded genes between pathogens and commensals fostering the spread of fitness-, virulence-, and antibiotic-resistance determinants.
BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus
Authors: Jeanneteau Freddy D. , Lambert W. Marcus , Ismaili Naima , Bath Kevin G. , Lee Francis S. , Garabedian Michael J. , Chao Moses V.
Published: January 2012

Regulation of the hypothalamic–pituitary–adrenal (HPA) axis is critical for adaptation to environmental changes. The principle regulator of the HPA axis is corticotrophin-releasing hormone (CRH), which is made in the parventricular nucleus and is an important target of negative feedback by glucocorticoids. However, the molecular mechanisms that regulate CRH are not fully understood. Disruption of normal HPA axis activity is a major risk factor of neuropsychiatric disorders in which decreased expression of the glucocorticoid receptor (GR) has been documented. To investigate the role of the GR in CRH neurons, we have targeted the deletion of the GR, specifically in the parventricular nucleus. Impairment of GR function in the parventricular nucleus resulted in an enhancement of CRH expression and an up-regulation of hypothalamic levels of BDNF and disinhibition of the HPA axis. BDNF is a stress and activity-dependent factor involved in many activities modulated by the HPA axis. Significantly, ectopic expression of BDNF in vivo increased CRH, whereas reduced expression of BDNF, or its receptor TrkB, decreased CRH expression and normal HPA functions. We find the differential regulation of CRH relies upon the cAMP response-element binding protein coactivator CRTC2, which serves as a switch for BDNF and glucocorticoids to direct the expression of CRH.
Underground leaves ofPhilcoxiatrap and digest nematodes
Authors: Pereira Caio G. , Almenara Daniela P. , Winter Carlos E. , Fritsch Peter W. , Lambers Hans , Oliveira Rafael S.
Published: January 2012

The recently described genusPhilcoxiacomprises three species restricted to well lit and low-nutrient soils in the Brazilian Cerrado. The morphological and habitat similarities ofPhilcoxiato those of some carnivorous plants, along with recent observations of nematodes over its subterranean leaves, prompted the suggestion that the genus is carnivorous. Here we report compelling evidence of carnivory inPhilcoxiaof the Plantaginaceae, a family in which no carnivorous members are otherwise known. We also document both a unique capturing strategy for carnivorous plants and a case of a plant that traps and digests nematodes with underground adhesive leaves. Our findings illustrate how much can still be discovered about the origin, distribution, and frequency of the carnivorous syndrome in angiosperms and, more generally, about the diversity of nutrient-acquisition mechanisms that have evolved in plants growing in severely nutrient-impoverished environments such as the Brazilian Cerrado, one of the world's 34 biodiversity hotspots.
Virulence determinants in the obligate intracellular pathogen
Chlamydia trachomatis
revealed by forward genetic approaches
Authors: Nguyen Bidong D. , Valdivia Raphael H.
Published: January 2012

Chlamydia trachomatis
, a pathogen responsible for diseases of significant clinical and public health importance, remains poorly characterized because of its intractability to routine molecular genetic manipulation. We have developed a combinatorial approach to rapidly generate a comprehensive library of genetically defined mutants. Chemical mutagenesis, coupled with whole-genome sequencing (WGS) and a system for DNA exchange within infected cells, was used to generate
Chlamydia
mutants with distinct phenotypes, map the underlying genetic lesions, and generate isogenic strains. As a result, we identified mutants with altered glycogen metabolism, including an attenuated strain defective for type II secretion. The coupling of chemically induced gene variation and WGS to establish genotype–phenotype associations should be broadly applicable to the large list of medically and environmentally important microorganisms currently intractable to genetic analysis.
Indirect evidence that maternal microchimerism in cord blood mediates a graft-versus-leukemia effect in cord blood transplantation
Authors: van Rood Jon J. , Scaradavou Andromachi , Stevens Cladd E.
Published: January 2012

During pregnancy women can develop B- and T-cell immunity against the inherited paternal antigens (IPAs) of the fetus, such as HLA, peptides of minor histocompatibilty antigens, and possibly onco-fetal antigens. The biological and pathological role of these pregnancy-induced immunological events is only understood in part. However, anti-IPA immunity in the mother persists for many decades after delivery and may reduce relapse in offspring with leukemia after HLA-haploidentical transplantation of maternal hematopoietic stem cells (HSC). We hypothesized that maternal anti-IPA immune elements cross the placenta and might confer a potent graft-versus-leukemia effect when cord blood (CB) is used in unrelated HSC transplantation. In a retrospective study of single-unit CB recipients with all grafts provided by the New York Blood Center, we show that patients with acute myeloid or lymphoblastic leukemia (
n
= 845) who shared one or more HLA-A, -B, or -DRB1 antigens with their CB donor's IPAs had a significant decrease in leukemic relapse posttransplantation [hazard ratio (HR) = 0.38,
P
< 0.001] compared with those that did not. Remarkably, relapse reduction in patients receiving CB with one HLA mismatch (HR = 0.15,
P
< 0.001) was not associated with an increased risk of severe acute graft-versus-host disease (HR = 1.43,
P
= 0.730). Our findings may explain the unexpected low relapse rate after CB transplantation, open new avenues in the study of leukemic relapse after HSC transplantation (possibly of malignancies in general), and have practical implications for CB unit selection.
Ablation of neurons expressing agouti-related protein, but not melanin concentrating hormone, in leptin-deficient mice restores metabolic functions and fertility
Authors: Wu Qi , Whiddon Benjamin B. , Palmiter Richard D.
Published: January 2012

Leptin-deficient (

Lep
ob/ob

) mice are obese, diabetic, and infertile. Ablation of neurons that make agouti-related protein (AgRP) in moderately obese adult

Lep
ob/ob

mice caused severe anorexia. The mice stopped eating for 2 wk and then gradually recovered. Their body weight fell to within a normal range for WT mice, at which point food intake and glucose tolerance were restored to that of WT mice. Remarkably, both male and female

Lep
ob/ob

mice became fertile. Ablation of neurons that express melanin-concentrating hormone (MCH) in adult

Lep
ob/ob

mice had no effect on food intake, body weight, or fertility, but resulted in improved glucose tolerance. We conclude that AgRP-expressing neurons play a critical role in mediating the metabolic syndrome and infertility of

Lep
ob/ob

mice, whereas MCH-expressing neurons have only a minor role.
Uric acid stones in the urinary bladder of aryl hydrocarbon receptor (AhR) knockout mice
Authors: Butler Ryan , Inzunza Jose , Suzuki Hitoshi , Fujii-Kuriyama Yoshiaki , Warner Margaret , Gustafsson Jan-Åke
Published: January 2012

The aryl hydrocarbon receptor (AhR) knockout mice raised in the laboratory of Fujii-Kuriyama have been under investigation for several years because of the presence in their urinary bladder of large, yellowish stones. The stones are composed of uric acid and become apparent in the bladders as tiny stones when mice are 10 wk of age. By the time the mice are 6 mo of age, there are usually two or three stones with diameters of 3–4 mm. The urate concentration in the serum was normal but in the urine the concentration was 40–50 mg/dL, which is 10 times higher than that in the WT littermates. There were no apparent histological pathologies in the kidney or joints and the levels of enzymes involved in elimination of purines were normal. The source of the uric acid was therefore judged to be from degradation of nucleic acids due to a high turnover of cells in the bladder itself. The bladder was fibrotic and the luminal side of the bladder epithelium was filled with eosinophilic granules. There was loss of E-cadherin between some epithelial cells, with an enlarged submucosal area filled with immune cells and sometimes invading epithelial cells. We hypothesize that in the absence of AhR there is loss of detoxifying enzymes, which leads to accumulation of unconjugated cytotoxins and carcinogens in the bladder. The presence of bladder toxins may have led to the increased apoptosis and inflammation as well as invasion of epithelial cells in the bladders of older mice.
Decreased adrenergic tone in acromegaly: evidence from direct recording of muscle sympathetic nerve activity
Authors: Seravalle G. , Carzaniga C. , Attanasio R. , Grassi G. , Lonati L. , Facchini C. , Cozzi R. , Fatti L. M. , Montini M. , Vitale G. , Sciortino G. , Damanti S. , Brambilla G. , Cavagnini F. , Mancia G. , Scacchi M.
Published: January 2012

Objective

Sympathovagal imbalance has been shown in acromegaly by indirect measurements of adrenergic tone. Data regarding direct measurement of sympathetic activity are lacking as yet. Aim of this study was to assess the adrenergic tone through direct recording of muscle sympathetic nerve activity (MSNA) in acromegalic patients.

Design

Fifteen patients (age 26–66 years, eight women) with newly diagnosed active acromegaly without hyperprolactinaemia, pituitary hormone deficiencies, obstructive sleep apnoea and cardiac hypertrophy, and 15 healthy subjects matched for age, sex and body mass index were recruited. After evaluating anthropometric and echocardiographic parameters, anterior pituitary function, glucose and lipid metabolism, and measuring plasma leptin, direct recording of sympathetic outflow via the microneurographic technique was performed.

Results

For similar anthropometric and metabolic parameters in patients and controls, HOMA index was significantly increased in the former (4·2 ± 2·39 vs 1·6 ± 0·19, P < 0·001). Surprisingly, this finding of insulin resistance was accompanied by a marked sympathetic inhibition (MSNA 18·3 ± 8·10 vs 37·3 ± 6·48 bursts/min, P < 0·0001, respectively in patients and controls). A reduction in plasma leptin (1·6 ± 1·04 vs 6·5 ± 2·01 μg/l, P < 0·0001) was also recorded in the patients. MSNA was positively correlated with leptin (P < 0·0001).

Conclusions

Newly diagnosed acromegalic patients without cardiac hypertrophy display a decreased sympathetic outflow in spite of insulin resistance. This finding might be related to hypoleptinaemia.
Impact factor in cytopathology journals: what does it reflect and how much does it matter?
Authors: AbdullGaffar B.
Published: January 2012

B. AbdullGaffar  Impact factor in cytopathology journals: what does it reflect and how much does it matter?

Objective:  To study the trends of impact factor (IF) in four cytopathology journals. To investigate the factors that might influence IF in cytopathology literature and whether IF has any impact on cytopathology practice.

Methods:  The IFs of four cytopathology journals were searched from 2005 to 2009. The IFs and their relationships with the types and number of publications, publishers, the official societies, readership, the quality of their contents, the topics covered and the levels of evidence were compared.

Results:  Cancer Cytopathology (CC) had the highest IF. Acta Cytologica (AC) had the lowest IF, which appeared to be in decline. Cytopathology (C) and Diagnostic Cytopathology (DC) had a slow but steady increase in their IF. Components that might influence these differences could include the category and the society of the journal, targeted readers and certain types of publications. Publishers, the number of publications, the types of topics covered and the levels of evidence probably have no major effect on IF.

Conclusions:  IF has its own benefits and original applications. IF is a quantitative measure that does not reflect the levels of evidence in cytopathology journals. IF should not be abandoned because it might encourage competition between cytopathology journals, but it should not dictate their contents.
Cytokine expression in response to root canal infection in gnotobiotic mice
Authors: Maciel K. F. , Neves de Brito L. C. , Tavares W. L. F. , Moreira G. , Nicoli J. R. , Vieira L. Q. , Ribeiro Sobrinho A. P.
Published: January 2012

Maciel KF, Neves de Brito LC, Tavares WLF, Moreira G, Nicoli JR, Vieira LQ, Ribeiro Sobrinho AP. Cytokine expression in response to root canal infection in gnotobiotic mice. International Endodontic Journal, 45, 354–362, 2012.

Aim  To examine cytokine expression profiles during periapical lesion development in response to synergetic human pathogens in a gnotobiotic mouse model.

Methodology  Human strains of Fusobacterium nucleatum and Peptostreptococcus prevotii were inoculated into the root canals of germ‐free mice in either mono‐ or bi‐association. Animals were killed 7 and 14 days after infection, and periapical tissues were collected. mRNA expression of the cytokines IFN‐γ, TNF‐α, Receptor activator of nuclear factor kappa‐B ligand (RANKL), IL‐10, IL‐4 and transforming growth factor β (TGF‐β) was assessed using real‐time PCR. Levene’s test was used to assess the equality of variance of the data, whereas a t‐test for independent samples was used to evaluate the significance of the differences between groups (P < 0.05).

Results  The mRNA expression of IFN‐γ and TNF‐α was up‐regulated by F. nucleatum during the acute (day 7) and chronic phase (day 14) of periapical lesion development. However, in bi‐infection the expression of IFN‐γ and TNF‐α were effectively absent at both time‐points. RANKL mRNA expression was down‐regulated during dual infection at the chronic phase. As IL‐4 expression was similar at both time‐points, IL‐4 does not appear to be involved in the periapical response to these bacterial strains. IL‐10 was up‐regulated during the chronic phase by mono‐infection with either F. nucleatum or P. prevotii. Dual infection increased TGF‐β mRNA expression on day 7, which paralleled the decrease in IFN‐γ and TNF‐α mRNA levels at the same time‐point. F. nucleatum increased TGF‐β mRNA expression during the chronic phase.

Conclusion  Cytokine profiles depend on the nature of the bacterial challenge. Both TGF‐β and IL‐10 appeared to be regulating the proinflammatory cytokine responses at both time‐points of the periapical immune response.
Randomized controlled trial of a lay‐facilitated angina management programme
Authors: Furze Gill , Cox Helen , Morton Veronica , Chuang Ling‐Hsiang , Lewin Robert J.P. , Nelson Pauline , Carty Richard , Norris Heather , Patel Nicky , Elton Peter
Published: January 2012

furze g., cox h., morton v., chuang l.‐h., lewin r.j.p., nelson p., carty r., norris h., patel n. & elton p. (2012) Randomized controlled trial of a lay‐facilitated angina management programme. Journal of Advanced Nursing68(10), 2267–2279.

Aims.  This article reports a randomized controlled trial of lay‐facilitated angina management (registered trial acronym: LAMP).

Background.  Previously, a nurse‐facilitated angina programme was shown to reduce angina while increasing physical activity, however most people with angina do not receive a cardiac rehabilitation or self‐management programme. Lay people are increasingly being trained to facilitate self‐management programmes.

Design.  A randomized controlled trial comparing a lay‐facilitated angina management programme with routine care from an angina nurse specialist.

Methods.  Participants with new stable angina were randomized to the angina management programme (intervention: 70 participants) or advice from an angina nurse specialist (control: 72 participants). Primary outcome was angina frequency at 6 months; secondary outcomes at 3 and 6 months included: risk factors, physical functioning, anxiety, depression, angina misconceptions and cost utility. Follow‐up was complete in March 2009. Analysis was by intention‐to‐treat; blind to group allocation.

Results.  There was no important difference in angina frequency at 6 months. Secondary outcomes, assessed by either linear or logistic regression models, demonstrated important differences favouring the intervention group, at 3 months for: Anxiety, angina misconceptions and for exercise report; and at 6 months for: Anxiety; Depression; and angina misconceptions. The intervention was considered cost‐effective.

Conclusion.  The angina management programme produced some superior benefits when compared to advice from a specialist nurse.
Topical herbal application as an adjuvant treatment for chronic kidney disease – a systematic review of randomized controlled clinical trials
Authors: Zhang Hongwei , Ho Yi Fong , Che Chun‐Tao , Lin Zhi‐Xiu , Leung Connie , Chan Lai Sum
Published: January 2012

zhang h., ho y.f., che c.‐t., lin z.‐x., leung c. & chan l.s. (2012) Topical herbal application as an adjuvant treatment for chronic kidney disease – a systematic review of randomized controlled clinical trials. Journal of Advanced Nursing68(6), 1679–1691.

Aim.  To report a systematic review to evaluate whether topical herbal medicine delays the progress of renal disease and improves its complications in people with chronic kidney disease.

Background.  Besides dialysis or renal transplantation, patients with chronic kidney disease, especially those with insufficient renal function, are in a great need of effective conservative treatment methods. Topical application of herbal medicine, a common treatment modality in China, has been found in some clinical studies to benefit the patients with chronic kidney disease.

Data sources.  The English databases including CENTRAL (February 2010), Medline (1950 to February 2010), EMBASE (1980 to February 2010), and AMED (1985 to January 2010), and several Chinese databases covering the period of 1949 to February 2010 were searched for randomized controlled trials that compared external use of herbal medicine with no treatment, placebo, or conventional treatment for chronic kidney disease and its complications.

Review methods.  We undertook a systematic review and meta‐analysis following Cochrane processes.

Results.  Twenty‐three trials with a total of 1057 patients were included. Their results suggest that herbal paste and bathing or fuming treatment might have a beneficial effect in terms of delaying the progress of renal disease, improving kidney function, and ameliorating some kidney complications in patients with chronic kidney disease. However, the low quality and poor reporting practices of the studies covered led to no definitive conclusion.

Conclusion.  Further larger and more rigorously designed clinical trials with proper outcome measures are needed to confirm the findings.
TbPIF8, a Trypanosoma brucei protein related to the yeast Pif1 helicase, is essential for cell viability and mitochondrial genome maintenance
Authors: Wang Jianyang , Englund Paul T. , Jensen Robert E.
Published: January 2012

The trypanosome mitochondrial genome, kinetoplast DNA (kDNA), is a massive network of interlocked DNA rings, including several thousand minicircles and dozens of maxicircles. The unusual complexity of kDNA would indicate that numerous proteins must be involved in its condensation, replication, segregation and gene expression. During our investigation of trypanosome mitochondrial PIF1‐like helicases, we found that TbPIF8 is the smallest and most divergent. It lacks some conserved helicase domains, thus implying that unlike other mitochondrial PIF1‐like helicases, this protein may have no enzymatic activity. TbPIF8 is positioned on the distal face of kDNA disk and its localization patterns vary with different kDNA replication stages. Stem‐loop RNAi of TbPIF8 arrests cell growth and causes defects in kDNA segregation. RNAi of TbPIF8 causes only limited kDNA shrinkage but the networks become disorganized. Electron microcopy of thin sections of TbPIF8‐depleted cells shows heterogeneous electron densities in the kinetoplast disk. Although we do not yet know its exact function, we conclude that TbPIF8 is essential for cell viability and is important for maintenance of kDNA.
Light‐dependent and asynchronous replication of cyanobacterial multi‐copy chromosomes
Authors: Watanabe Satoru , Ohbayashi Ryudo , Shiwa Yuh , Noda Aska , Kanesaki Yu , Chibazakura Taku , Yoshikawa Hirofumi
Published: January 2012

While bacteria such as Escherichia coli and Bacillus subtilis harbour a single circular chromosome, some freshwater cyanobacteria have multiple chromosomes per cell. The detailed mechanism(s) of cyanobacterial replication remains unclear. To elucidate the replication origin (ori), form and synchrony of the multi‐copy genome in freshwater cyanobacteria Synechococcus elongatus PCC 7942 we constructed strain S. 7942TK that can incorporate 5‐bromo‐2'‐deoxyuridine (BrdU) into genomic DNA and analysed its de novo DNA synthesis. The uptake of BrdU was blocked under dark and resumed after transfer of the culture to light conditions. Mapping analysis of nascent DNA fragments using a next‐generation sequencer indicated that replication starts bidirectionally from a single ori, which locates in the upstream region of the dnaN gene. Quantitative analysis of BrdU‐labelled DNA and whole‐genome sequence analysis indicated that the peak timing of replication precedes that of cell division and that replication is initiated asynchronously not only among cell populations but also among the multi‐copy chromosomes. Our findings suggest that replication initiation is regulated less stringently in S. 7942 than in E. coli and B. subtilis.
Alloreactivity: An Old Puzzle Revisited
Authors: Nagy Z. A.
Published: January 2012

Alloreactivity, defined as a strong primary T cell response against allelic variants of major histocompatibility complex (MHC) molecules in the species, has been a long‐standing puzzle in immunology with some of its details remaining unclear up to now. Here I shall provide a historical overview of how our understanding of alloreactivity has evolved and propose an interpretation that considers alloreactivity to be a mixture of four mechanistically distinct prototypes of T cell response, namely, self‐restricted peptide specific, allorestricted peptide specific, alloreactive peptide dependent and alloreactive peptide independent. The relative contribution of each prototype to a given alloresponse is dependent on the extent of disparity (i.e. the number and nature of amino acid substitutions in the docking surface for T cell receptor) between the MHC molecule that the T cell recognizes as self and the stimulating MHC molecule.
Childhood adrenocortical carcinoma as a sentinel cancer for detecting families with germline TP53 mutations
Authors: Choong SS , Latiff ZA , Mohamed M , Lim LLW , Chen KS , Vengidasan L , Razali H , Abdul Rahman EJ , Ariffin H ,   for Malaysian Society of Paediatric Haematology‐Oncology
Published: January 2012

Choong SS, Latiff ZA, Mohamed M, Lim LLW, Chen KS, Vengidasan L, Razali H, Abdul Rahman EJ, Ariffin H for Malaysian Society of Paediatric Haematology‐Oncology. Childhood adrenal cortical carcinoma as a sentinel cancer for detecting families with germline TP53 mutations.

Li‐Fraumeni syndrome (LFS) is a highly penetrant, autosomal dominant disorder where affected individuals carry a 50% risk of developing cancer before 30 years of age. It is most commonly associated with mutations in the tumour suppressor gene, TP53. Adrenocortical carcinoma (ACC) is a very rare paediatric cancer, and up to 80% of affected children are found to carry germline TP53 mutations. Hence, we propose using childhood ACC incidence as selection criteria for referral for TP53 mutation testing, independent of familial cancer history. Under the auspices of the Malaysian Society of Paediatric Haematology–Oncology, four eligible children diagnosed with ACC over a 30‐month study period were referred for mutation testing. Three had a germline TP53 mutation. Subsequent TP53 testing in relatives showed two inherited mutations and one de novo mutation. These findings strongly support paediatric ACC as a useful sentinel cancer for initiating a germline TP53/LFS detection programme, particularly in countries where the lack of structured oncogenetic practice precludes the identification of families with LFS features.
Female factor IX deficiency due to maternally inherited X‐inactivation
Authors: Esquilin JM , Takemoto CM , Green NS
Published: January 2012

Esquilin JM, Takemoto CM, Green, NS. Female factor IX deficiency due to maternally inherited X‐inactivation.

X‐chromosome inactivation is normally a random event that is regulated by the X chromosome itself. Rarely, females are affected by X‐linked disorders from extremely skewed X‐chromosome inactivation. Here, we report a family with hemophilia B with female expression through inherited X skewing that appears to be independent of either X chromosome. This finding suggests the possibility of a dominant autosomal contribution to inherited skewed X inactivation.
Complete Nucleotide Sequence of the RNA 3 of Bacopa chlorosis virus and Production of Polyclonal Antibodies to a Recombinant Coat Protein
Authors: Menzel Wulf , Hamacher Joachim , Weissbrodt Sandra , Winter Stephan
Published: January 2012

The complete sequence of the RNA 3 of a virus causing chlorosis in Impatiens in Germany was determined and identified as an isolate of Bacopa chlorosis virus (BaCV, genus Ilarvirus). BaCV has previously only been reported from bacopa in the USA, but no coat protein (CP) sequence has been previously available. Both RNA 3 encoded proteins, CP and movement protein, showed highest sequence identity to Parietaria mottle virus, a subgroup 1 ilarvirus. Attempts to purify BaCV failed, so an antiserum was raised against a recombinant CP. The polyclonal antiserum so produced allowed specific detection of BaCV but showed no serological cross‐reaction with other ilarviruses and was unsuitable for immunoelectron microscopy. The host range includes many important flowering plant species, highlighting the potential threat BaCV might pose for the horticultural industry. This is the first report of BaCV occurring in Germany and outside the US.
Expression analysis of abiotic stress‐responsive genes in two rice heterotic crosses under cold, heat and drought stresses
Authors: Song Shufeng , Li Li , Yang Xiping , Fu Xiqin , Xu Mengliang , Rocha Pedro , Xia Xinjie
Published: January 2012

With 6 figures and 4 tables

Heterosis refers to the phenomenon in which the hybrid progeny of two inbred varieties exhibits enhanced growth or agronomic performance. Although a century‐long history of research has generated several hypotheses regarding the genetic basis of heterosis, the molecular mechanisms underlying heterosis and heterotic gene activity remain elusive. In this study, two rice heterotic crosses PA64S×93‐11 and Y58S×93‐11 were used as plant materials to analyse the activities of 10 abiotic stress‐responsive genes under cold, heat and drought stresses by quantitative real‐time PCR. The obtained result demonstrated that the expression levels of genes analysed in hybrids is unexpectedly higher, compared to those of both parental lines. More than 50% of the cases displayed over‐parent expression levels. The combined allelic expression pattern was found in hybrid, and under different stress conditions, different alleles were differentially expressed in hybrid.
Characterization and mapping of Lr65 in spelt wheat ‘Altgold Rotkorn’
Authors: Mohler Volker , Singh Davinder , Singrün Charlotte , Park Robert F.
Published: January 2012

With 1 figure and 4 tables

A leaf rust resistance gene (temporarily designated LrARK0;) was identified in the Swiss spelt wheat ‘Altgold Rotkorn’ and mapped to chromosome 2A. The gene was located 2 cM distal to marker Xgwm614 (co‐segregating with markers Xbarc124, Xbarc212, XE34M48‐103 and XE38M53‐334) on chromosome 2AS. This map location is similar to that of LrAlt identified in the same germplasm in a previous study. Based on gene location, allelism tests and pathogen specificity, this leaf rust resistance gene was designated Lr65. A single gene stock (AUS 91455) in a Triticum aestivum background was developed and registered for utilization and research purposes. The gene was widely effective against Australian and German isolates of Puccinia triticina.
Genetic improvement of grass pea (Lathyrus sativus) in Ethiopia: an unfulfilled promise
Authors: Girma Dejene , Korbu Lijalem
Published: January 2012

With 5 figures and 3 tables

Grass pea (Lathyrus sativus L.) is an important crop in Ethiopia. Its vital importance in the Ethiopian agriculture emanates from its resistance to drought, salinity, waterlogging and low soil fertility. However, low levels of the amino acids methionine and tryptophan and the presence of the neurotoxin β‐N‐oxalyl‐L‐α,β‐diaminopropanoic acid (ODAP) in the seeds are the major limitations of the crop. Genetic improvement of grass pea in Ethiopia has been started in the 1960s at Holetta Agricultural Research Center. The major objectives of the grass pea research were to develop and promote high‐yielding cultivars with low ODAP content coupled with improved management production packages. However, the 50 years of on‐station and on‐farm research was not successful in producing outstanding varieties with the desired traits. Compared to other grain legumes, the poor success of varietal development endeavours within the context of grass pea improvement philosophy is typically related to the failure of the conventional breeding approach to fix a zero or low ODAP content because this trait is highly influenced by climatic and edaphic environment.
Mapping QTL for Fusarium wilt Race 2 partial resistance in pea (Pisum sativum)
Authors: Mc Phee Kevin E. , Inglis Debbie A. , Gundersen Babette , Coyne Clarice J.
Published: January 2012

With 3 figures and 4 tables

Fusarium oxysporum f.sp. pisi (Fop) exists in pea production regions worldwide and causes a vascular wilt resulting in significant crop losses. Four races of Fop have been identified, and resistance to each was reportedly conferred by an individual single dominant gene. Fnw confers resistance to Fop race 2, which can be a serious pathogen for both green and dry pea production in the Pacific Northwest region of the United States. The objectives of this research were to (i) place Fnw on the Pisum genetic map, (ii) detect additional genetic factors associated with resistance to race 2 and (iii) identify closely linked markers for use in pea breeding A recombinant inbred line (RIL) population of 187 F7‐derived lines from the cross ‘Shawnee’/‘Bohatyr’ was developed by single‐seed decent. All 187 RILs, the parents and one set of race 2 pea differential entries were inoculated with Fop race 2 under controlled conditions in three experiments, each with two or three replications per entry. Disease reactions were recorded as percentage diseased plants 10–14 days postinoculation or at regular intervals through flowering or early pod fill. Data for progressive wilting over time, typical of Fop race 2, were used to calculate area under disease progress curve (AUDPC) values. Data for percentage diseased plants placed the putative single gene Fnw on Pisum sativum linkage group IV, with LOD scores ranging from 40.0 to 65.6 and minor loci on LG III (LOD 3.97 and 4.60). AUDPC values allowed for the detection of additional QTL on linkage group III with LOD scores of 3.97 and 4.60. The presence of recombinants in the population indicated that complementary genes were contributed by each parent, both of which showed intermediate reaction to Fop race 2. Results of this research provide a basis for marker‐assisted selection of the major Fnw loci in both green and dry pea breeding programmes, but additional research is necessary to fully characterize the complementary gene action governing resistance of the two minor loci identified.
Factors affecting independence in eating among elderly with Alzheimer's disease
Authors: Edahiro Ayako , Hirano Hirohiko , Yamada Ritsuko , Chiba Yumi , Watanabe Yutaka , Tonogi Morio , Yamane Gen‐yuki
Published: January 2012

Aim:  In elderly patients with dementia, disturbed eating behavior is understood to be a core symptom or a behavioral and psychological symptom of dementia (BPSD). The purpose of the present study was to investigate the factors affecting self‐feeding in elderly patients with Alzheimer's disease (AD).

Methods:  A total of 150 AD patients who were hospitalized in dementia wards, or were residents of institutions or group homes were enrolled. The patients underwent an eating behavior examination, cognitive assessment, neurological examination and vital function tests. The eating behavior examination consisted of observation of the patients at mealtime. Items assessing eating behavior included the number of feeding cycles, stopping of eating or agitation and dysfunction.

Results:  Logistic regression analysis carried out to identify factors with a significant effect on decreased independence in eating were difficulty in beginning a meal (OR = 14.498, CI = 2.067–101.690), presence of dysphagia signs (OR = 5.214, CI = 1.031–26.377) and the severity of dementia (OR = 4.538, CI = 1.154–17.843).

Conclusion:  The present study is the first to generate objective data showing that difficulty in beginning a meal is a factor that hinders independence in eating in AD, in addition to the presence of dysphagia signs and the severity of dementia. Assisting AD patients in maintaining eating independence might be effectively achieved by eliminating environmental factors that interfere with beginning a meal, and by providing assistance that will promote beginning a meal. The present results show the necessity of developing effective methods for assisting elderly patients with AD. Geriatr Gerontol Int 2012; 12: 481–490.
Association between polypharmacy and dementia in older people: A population‐based case–control study in Taiwan
Authors: Lai Shih‐Wei , Lin Chih‐Hsueh , Liao Kuan‐Fu , Su Li‐Ting , Sung Fung‐Chang , Lin Cheng‐Chieh
Published: January 2012

Aim:  The aim of the present study was to investigate whether polypharmacy correlates with the risk of dementia in older people.

Methods:  From representative claims data established from the National Health Insurance with a population coverage rate of 99% in Taiwan, we identified 7135 newly diagnosed patients with dementia in 2000–2008 and 2 8540 randomly selected controls without dementia, both aged ≥65 years. The daily use of prescribed drugs in the past 2 years was compared between cases and controls, controlling for demographic characters and comorbidities.

Results:  The incidence of dementia increased with the number of medications used and age. Cases were older than controls, predominant with women and more likely to use five or more drugs daily (44.0% vs 32.0%, P < 0.0001). Multivariate logistic regression analysis showed that, compared with participants using zero to one drug, the odds ratios (OR) of dementia were 1.28 (95% confidence interval [CI] 1.18–1.38) for those using two to four drugs, 1.34 (95% CI 1.23–1.46) for those using five to nine drugs and 1.56 (95% CI 1.38–1.76) for those using 10 or more drugs. Cerebrovascular disease (OR 3.19), diabetes mellitus (OR 1.23), chronic kidney disease (OR 1.21) and hypertension (OR 1.08) were significant comorbidities predicting the risk of dementia. There was significant interaction between cerebrovascular disease and the number of medications used in the dementia risk.

Conclusions:  The risk of dementia increases steadily with the number of medications used and age in older people in Taiwan. Cerebrovascular disease, diabetes mellitus, chronic kidney disease and hypertension might also correlate with the risk of dementia. Geriatr Gerontol Int 2012; 12: 491–498.