bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing morphological complexity in multiple parallel lineages of the Crustacea
Authors: Adamowicz Sarah J. , Purvis Andy , Wills Matthew A.
Published: March 2008

The prospect of finding macroevolutionary trends and rules in the history of life is tremendously appealing, but very few pervasive trends have been found. Here, we demonstrate a parallel increase in the morphological complexity of most of the deep lineages within a major clade. We focus on the Crustacea, measuring the morphological differentiation of limbs. First, we show a clear trend of increasing complexity among 66 free-living, ordinal-level taxa from the Phanerozoic fossil record. We next demonstrate that this trend is pervasive, occurring in 10 or 11 of 12 matched-pair comparisons (across five morphological diversity indices) between extinct Paleozoic and related Recent taxa. This clearly differentiates the pattern from the effects of lineage sorting. Furthermore, newly appearing taxa tend to have had more types of limbs and a higher degree of limb differentiation than the contemporaneous average, whereas those going extinct showed higher-than-average limb redundancy. Patterns of contemporary species diversity partially reflect the paleontological trend. These results provide a rare demonstration of a large-scale and probably driven trend occurring across multiple independent lineages and influencing both the form and number of species through deep time and in the present day.
Linking Notch signaling to ischemic stroke
Authors: Arboleda-Velasquez Joseph F. , Zhou Zhipeng , Shin Hwa Kyoung , Louvi Angeliki , Kim Hyung-Hwan , Savitz Sean I. , Liao James K. , Salomone Salvatore , Ayata Cenk , Moskowitz Michael A. , Artavanis-Tsakonas Spyros
Published: March 2008

Vascular smooth muscle cells (SMCs) have been implicated in the pathophysiology of stroke, the third most common cause of death and the leading cause of long-term neurological disability in the world. However, there is little insight into the underlying cellular pathways that link SMC function to brain ischemia susceptibility. Using a hitherto uncharacterized knockout mouse model of
Notch 3
, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover a striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype.
The non-Anglophone scholar on the periphery of scholarly publication
Authors: Flowerdew John
Published: March 2008

As a symptom of globalization and the marketization of the universities, more and more scholars, many or most, of whom use English as an additional language (EAL), are being required to published in English. This article presents some qualitative data which highlights some of the difficulties encountered by such writers. It first discusses a previously published case study of an EAL writer writing for publication, highlighting some of the difficulties encountered by this young scholar. It then goes on to consider a particular writing strategy adopted by some EAL writers which might be considered to be controversial, the copying of fragments of text from previously published work, and referred to here as language reuse. The final part of the paper discusses various approaches directed towards alleviating problems encountered by EAL writers such as those exemplified in the main body of the paper.
Is a holistic protolanguage a plausible precursor to language?
Authors: Smith Kenny
Published: March 2008

If protolanguage was a holistic system where complex meanings were conveyed using unanalysed forms, there must be some process (analysis) which delivered up the elements of modern language from this system. This paper draws on evidence from computational modelling, developmental and historical linguistics and comparative psychology to evaluate the plausibility of the analysis process. While some of the criticisms levelled at analysis can be refuted using such evidence, several areas are highlighted where further evidence is required to decide key issues. More generally, the debate over the nature of protolanguage offers a framework for developing and showcasing a modern, evidence-based evolutionary linguistics.
Protolanguage reconstructed
Authors: Smith Andrew D.M.
Published: March 2008

One important difference between existing accounts of protolanguage lies in their assumptions on the semantic complexity of protolinguistic utterances. I bring evidence about the nature of linguistic communication to bear on the plausibility of these assumptions, and show that communication is fundamentally inferential and characterised by semantic uncertainty. This not only allows individuals to maintain variation in linguistic representation, but also imposes a selection pressure that meanings be reconstructible from context. I argue that protolanguage utterances had varying degrees of semantic complexity, and developed into complex language gradually, through the same processes of re-analysis and analogy which still underpin continual change in modern languages.
Holophrasis and the protolanguage spectrum
Authors: Arbib Michael A.
Published: March 2008

Much of the debate concerning the question “Was Protolanguage Holophrastic?” assumes that protolanguage existed as a single, stable transitional form between communication systems akin to those of modern primates and human languages as we know them today. The present paper argues for a spectrum of protolanguages preceding modern languages emphasizing that (i) protospeech was intertwined with protosign and gesture; (ii) grammar emerged from a growing population of constructions; and (iii) an increasing protolexicon drove the emergence of phonological structure. This framework weakens arguments for the view that the earliest protolanguages were not holophrastic while advancing the claim that protolanguages became increasingly compositional over time en route to the emergence of true languages.
Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation
Authors: Toyo-oka Kazuhito , Mori Daisuke , Yano Yoshihisa , Shiota Masayuki , Iwao Hiroshi , Goto Hidemasa , Inagaki Masaki , Hiraiwa Noriko , Muramatsu Masami , Wynshaw-Boris Anthony , Yoshiki Atsushi , Hirotsune Shinji
Published: March 2008

Protein phosphatase 4 catalytic subunit (PP4c) is a PP2A-related protein serine/threonine phosphatase with important functions in a variety of cellular processes, including microtubule (MT) growth/organization, apoptosis, and tumor necrosis factor signaling. In this study, we report that NDEL1 is a substrate of PP4c, and PP4c selectively dephosphorylates NDEL1 at Cdk1 sites. We also demonstrate that PP4c negatively regulates Cdk1 activity at the centrosome. Targeted disruption of PP4c reveals disorganization of MTs and disorganized MT array. Loss of PP4c leads to an unscheduled activation of Cdk1 in interphase, which results in the abnormal phosphorylation of NDEL1. In addition, abnormal NDEL1 phosphorylation facilitates excessive recruitment of katanin p60 to the centrosome, suggesting that MT defects may be attributed to katanin p60 in excess. Inhibition of Cdk1, NDEL1, or katanin p60 rescues the defective MT organization caused by PP4 inhibition. Our work uncovers a unique regulatory mechanism of MT organization by PP4c through its targets Cdk1 and NDEL1 via regulation of katanin p60 distribution.
An interaction between the SRP receptor and the translocon is critical during cotranslational protein translocation
Authors: Jiang Ying , Cheng Zhiliang , Mandon Elisabet C. , Gilmore Reid
Published: March 2008

The signal recognition particle (SRP)–dependent targeting pathway facilitates rapid, efficient delivery of the ribosome–nascent chain complex (RNC) to the protein translocation channel. We test whether the SRP receptor (SR) locates a vacant protein translocation channel by interacting with the yeast Sec61 and Ssh1 translocons. Surprisingly, the slow growth and cotranslational translocation defects caused by deletion of the transmembrane (TM) span of yeast SRβ (SRβ-ΔTM) are exaggerated when the SSH1 gene is disrupted. Disruption of the SBH2 gene, which encodes the β subunit of the Ssh1p complex, likewise causes a growth defect when combined with SRβ-ΔTM. Cotranslational translocation defects in the ssh1ΔSRβ-ΔTM mutant are explained by slow and inefficient in vivo gating of translocons by RNCs. A critical function for translocation channel β subunits in the SR–channel interaction is supported by the observation that simultaneous deletion of Sbh1p and Sbh2p causes a defect in the cotranslational targeting pathway that is similar to the translocation defect caused by deletion of either subunit of the SR.
Distinct acto/myosin-I structures associate with endocytic profiles at the plasma membrane
Authors: Idrissi Fatima-Zahra , Grötsch Helga , Fernández-Golbano Isabel M. , Presciatto-Baschong Cristina , Riezman Howard , Geli María-Isabel
Published: March 2008

Endocytosis in yeast requires actin and clathrin. Live cell imaging has previously shown that massive actin polymerization occurs concomitant with a slow 200-nm inward movement of the endocytic coat (Kaksonen, M., Y. Sun, and D.G. Drubin. 2003. Cell. 115:475–487). However, the nature of the primary endocytic profile in yeast and how clathrin and actin cooperate to generate an endocytic vesicle is unknown. In this study, we analyze the distribution of nine different proteins involved in endocytic uptake along plasma membrane invaginations using immunoelectron microscopy. We find that the primary endocytic profiles are tubular invaginations of up to 50 nm in diameter and 180 nm in length, which accumulate the endocytic coat components at the tip. Interestingly, significant actin labeling is only observed on invaginations longer than 50 nm, suggesting that initial membrane bending occurs before initiation of the slow inward movement. We also find that in the longest profiles, actin and the myosin-I Myo5p form two distinct structures that might be implicated in vesicle fission.
Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine-phosphorylated caveolin-1
Authors: Goetz Jacky G. , Joshi Bharat , Lajoie Patrick , Strugnell Scott S. , Scudamore Trevor , Kojic Liliana D. , Nabi Ivan R.
Published: March 2008

Both tyrosine-phosphorylated caveolin-1 (pY14Cav1) and GlcNAc-transferase V (Mgat5) are linked with focal adhesions (FAs); however, their function in this context is unknown. Here, we show that galectin-3 binding to Mgat5-modified N-glycans functions together with pY14Cav1 to stabilize focal adhesion kinase (FAK) within FAs, and thereby promotes FA disassembly and turnover. Expression of the Mgat5/galectin lattice alone induces FAs and cell spreading. However, FAK stabilization in FAs also requires expression of pY14Cav1. In cells lacking the Mgat5/galectin lattice, pY14Cav1 is not sufficient to promote FAK stabilization, FA disassembly, and turnover. In human MDA-435 cancer cells, Cav1 expression, but not mutant Y14FCav1, stabilizes FAK exchange and stimulates de novo FA formation in protrusive cellular regions. Thus, transmembrane crosstalk between the galectin lattice and pY14Cav1 promotes FA turnover by stabilizing FAK within FAs defining previously unknown, interdependent roles for galectin-3 and pY14Cav1 in tumor cell migration.
Nuclear Dvl, c-Jun, β-catenin, and TCF form a complex leading to stabiLization of β-catenin–TCF interaction
Authors: Gan Xiao-qing , Wang Ji-yong , Xi Ying , Wu Zhi-li , Li Yi-ping , Li Lin
Published: March 2008

In canonical Wnt signaling, Dishevelled (Dvl) is a critical cytoplasmic regulator that releases β-catenin from degradation. Here, we find that Dvl and c-Jun form a complex with β-catenin–T-cell factor 4 (TCF-4) on the promoter of Wnt target genes and regulate gene transcription. The complex forms via two interactions of nuclear Dvl with c-Jun and β-catenin, respectively, both of which bind to TCF. Disrupting the interaction of Dvl with either c-Jun or β-catenin suppresses canonical Wnt signaling–stimulated transcription, and the reduction of Dvl diminished β-catenin–TCF-4 association on Wnt target gene promoters in vivo. Expression of a TCF-Dvl fusion protein largely rescued the c-Jun knockdown Wnt signaling deficiency in mammalian cells and zebrafish. Thus, we confirm that c-Jun functions in canonical Wnt signaling and show that c-Jun functions as a scaffold in the β-catenin–TCFs transcription complex bridging Dvl to TCF. Our results reveal a mechanism by which nuclear Dvl cooperates with c-Jun to regulate gene transcription stimulated by the canonical Wnt signaling pathway.
Dynamics of inner kinetochore assembly and maintenance in living cells
Authors: Hemmerich Peter , Weidtkamp-Peters Stefanie , Hoischen Christian , Schmiedeberg Lars , Erliandri Indri , Diekmann Stephan
Published: March 2008

To investigate the dynamics of centromere organization, we have assessed the exchange rates of inner centromere proteins (CENPs) by quantitative microscopy throughout the cell cycle in human cells. CENP-A and CENP-I are stable centromere components that are incorporated into centromeres via a “loading-only” mechanism in G1 and S phase, respectively. A subfraction of CENP-H also stays stably bound to centromeres. In contrast, CENP-B, CENP-C, and some CENP-H and hMis12 exhibit distinct and cell cycle–specific centromere binding stabilities, with residence times ranging from seconds to hours. CENP-C and CENP-H are immobilized at centromeres specifically during replication. In mitosis, all inner CENPs become completely immobilized. CENPs are highly mobile throughout bulk chromatin, which is consistent with a binding-diffusion behavior as the mechanism to scan for vacant high-affinity binding sites at centromeres. Our data reveal a wide range of cell cycle–specific assembly plasticity of the centromere that provides both stability through sustained binding of some components and flexibility through dynamic exchange of other components.
Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brain
Authors: Nezis Ioannis P. , Simonsen Anne , Sagona Antonia P. , Finley Kim , Gaumer Sébastien , Contamine Didier , Rusten Tor Erik , Stenmark Harald , Brech Andreas
Published: March 2008

p62 has been proposed to mark ubiquitinated protein bodies for autophagic degradation. We report that the Drosophila melanogaster p62 orthologue, Ref(2)P, is a regulator of protein aggregation in the adult brain. We demonstrate that Ref(2)P localizes to age-induced protein aggregates as well as to aggregates caused by reduced autophagic or proteasomal activity. A similar localization to protein aggregates is also observed in D. melanogaster models of human neurodegenerative diseases. Although atg8a autophagy mutant flies show accumulation of ubiquitin- and Ref(2)P-positive protein aggregates, this is abrogated in atg8a/ref(2)P double mutants. Both the multimerization and ubiquitin binding domains of Ref(2)P are required for aggregate formation in vivo. Our findings reveal a major role for Ref(2)P in the formation of ubiquitin-positive protein aggregates both under physiological conditions and when normal protein turnover is inhibited.
The role of CTCF in regulating nuclear organization
Authors: Williams Adam , Flavell Richard A.
Published: March 2008

The spatial organization of the genome is thought to play an important part in the coordination of gene regulation. New techniques have been used to identify specific long-range interactions between distal DNA sequences, revealing an ever-increasing complexity to nuclear organization. CCCTC-binding factor (CTCF) is a versatile zinc finger protein with diverse regulatory functions. New data now help define how CTCF mediates both long-range intrachromosomal and interchromosomal interactions, and highlight CTCF as an important factor in determining the three-dimensional structure of the genome.
Calcium-dependent Inactivation Terminates Calcium Release in Skeletal Muscle of Amphibians
Authors: Ríos Eduardo , Zhou Jingsong , Brum Gustavo , Launikonis Bradley S. , Stern Michael D.
Published: March 2008

In skeletal muscle of amphibians, the cell-wide cytosolic release of calcium that enables contraction in response to an action potential appears to be built of Ca2+ sparks. The mechanism that rapidly terminates this release was investigated by studying the termination of Ca2+ release underlying sparks. In groups of thousands of sparks occurring spontaneously in membrane-permeabilized frog muscle cells a complex relationship was found between amplitude a and rise time T, which in sparks corresponds to the active time of the underlying Ca2+ release. This relationship included a range of T where a paradoxically decreased with increasing T. Three different methods were used to estimate Ca2+ release flux in groups of sparks of different T. Using every method, it was found that T and flux were inversely correlated, roughly inversely proportional. A simple model in which release sources were inactivated by cytosolic Ca2+ was able to explain the relationship. The predictive value of the model, evaluated by analyzing the variance of spark amplitude, was found to be high when allowance was made for the out-of-focus error contribution to the total variance. This contribution was estimated using a theory of confocal scanning (Ríos, E., N. Shirokova, W.G. Kirsch, G. Pizarro, M.D. Stern, H. Cheng, and A. González. Biophys. J. 2001. 80:169–183), which was confirmed in the present work by simulated line scanning of simulated sparks. Considering these results and other available evidence it is concluded that Ca2+-dependent inactivation, or CDI, provides the crucial mechanism for termination of sparks and cell-wide Ca2+ release in amphibians. Given the similarities in kinetics of release termination observed in cell-averaged records of amphibian and mammalian muscle, and in spite of differences in activation mechanisms, CDI is likely to play a central role in mammals as well. Trivially, an inverse proportionality between release flux and duration, in sparks or in global release of skeletal muscle, maintains constancy of the amount of released Ca2+.
Abscess-forming lymphadenopathy and osteomyelitis in children with Bartonella henselae infection
Authors: Ridder-Schröter Regina , Marx Aleander , Beer Meinrad , Tappe Dennis , Kreth Hans-Wolfgang , Girschick Hermann J.
Published: March 2008

Bartonella henselaeis the agent of cat-scratch disease (CSD), a chronic lymphadenopathy among children and adolescents. A systemic infection is very rare and most of these cases are found in patients with immunodeficiency. Here, cases involving four children of 6–12 years of age are reported. Three of the children had an abscess-forming lymphadenopathy and surrounding myositis in the clavicular region of the upper arm. The diagnosis was made serologically and, in one case, using eubacterial universal PCR. One child was treated with erythromycin for 10 days, the second received cefotaxime and flucloxacillin for 14 days and the third child was not treated with antibiotics. The fourth child had a different course: a significantly elevated signal intensity affecting the complete humerus was found in magnetic resonance imaging, consistent with osteomyelitis. A lymph node abscess was also found in the axilla. Diagnosis was established by indirect fluorescence assay and lymph node biopsy. Antibiotic therapy using clarithromycin, clindamycin and rifampicin was gradually successful. Immunodeficiency was excluded. All described lesions healed without residues. In immunocompetent patients, infection affects skin and draining lymph nodes; however, prolonged fever of unknown origin as in the fourth patient indicated a systemic complication of CSD.
Anaplasma phagocytophilum infects cells of the megakaryocytic lineage through sialylated ligands but fails to alter platelet production
Authors: Granick Jennifer L. , Reneer Dexter V. , Carlyon Jason A. , Borjesson Dori L.
Published: March 2008

Anaplasma phagocytophilumis an obligate intracellular bacterial pathogen that principally inhabits neutrophils. However, infection withA. phagocytophilumresults in a moderate to marked thrombocytopenia. In host neutrophils,A. phagocytophilumuses sialylated ligands, primarily P-selectin glycoprotein ligand-1 (PSGL-1), to enter its host cell. PSGL-1 is expressed on a wide array of haematopoietic cells, including megakaryocytes. In this study, it was hypothesized that (i) cells of the megakaryocytic lineage (MEG-01 cells) would be susceptible toA. phagocytophiluminfection and (ii) infection may induce alterations in platelet production contributing to infection-induced thrombocytopenia. It was found that MEG-01 cells are susceptible to infection. MEG-01 cells expressing abundant sialylated ligands were the most susceptible to infection, and the absence of sialylation, or blocking of PSGL-1, limited infection susceptibility. However, infected MEG-01 cells produced proplatelets and platelet-like particles comparable to uninfected cells. These results highlight a novel target of pathogen infection and suggest that the pathogen may utilize similar strategies to gain access to megakaryocytes. Direct pathogen modification of platelet production may not play a role in infection-induced thrombocytopenia.
Central venous catheter infection associated with Pseudozyma aphidis in a child with short gut syndrome
Authors: Lin Shau-Shau , Pranikoff Thomas , Smith Shani F. , Brandt Mary E. , Gilbert Kemery , Palavecino Elizabeth L. , Shetty Avinash K.
Published: March 2008

Pseudozyma aphidis is a heterobasidiomycetous yeast related to the smut fungi in the genus Ustilago. Pseudozyma species are usually isolated from plants and rarely from clinical specimens. We report what is believed to be the first paediatric case of central venous catheter (CVC)-related fungaemia associated with P. aphidis. Prompt removal of the CVC in conjunction with anti-fungal therapy resulted in a successful outcome.
PCR-RFLP assay for species and subspecies differentiation of the Streptococcus bovis group based on groESL sequences
Authors: Chen Hsiao-Jan , Tsai Jui-Chang , Chang Tsung-Chain , Hung Wei-Chun , Tseng Sung-Pin , Hsueh Po-Ren , Teng Lee-Jene
Published: March 2008

The sequence diversity ofgroESLgenes amongStreptococcus bovisgroup isolates was analysed, including five reference strains and 36 clinical isolates. Phylogenetic analysis of thegroESandgroELsequences showed that the isolates that belonged to the same species or subspecies usually clustered together. The intergenic spacer region betweengroESandgroELwas variable in size (67–342 bp) and sequence and appeared to be a unique marker for species or subspecies determination. Sequence similarities of thegroESLgenes among species and subspecies ranged from 84.2 to 99.0 % ingroES, and from 88.0 to 99.0 % ingroEL. Based on the sequences determined, aStreptococcus bovisgroup-specific PCR assay was developed, which may provide an alternative means of distinguishing the bovis group from other viridans streptococci. Restriction digestion of the amplicon withAclI further differentiated the species and subspecies.
Linezolid lock prophylaxis of central venous catheter infection
Authors: Fennell Jérôme Patrick , O'Donohoe Martin , Cormican Martin , Lynch Maureen
Published: March 2008

Central venous catheter (CVC)-related infections are a major problem for patients requiring long-term venous access and may result in frequent hospital admissions and difficulties in maintaining central venous access. CVC-related blood stream infections are associated with increased duration of inpatient stay and cost approximately \#8364;13 585 per patient [Blot, S. I., Depuydt, P., Annemans, L., Benoit, D., Hoste, E., De Waele, J. J., Decruyenaere, J., Vogelaers, D., Colardyn, F. & Vandewoude, K. H. (2005). Clin Infect Dis
41, 1591–1598]. Antimicrobial lock therapy may prevent CVC-related blood stream infection, preserve central venous access and reduce hospital admissions. In this paper, the impact of linezolid lock prophylaxis in a patient with short bowel syndrome is described.
Dual regulation of interleukin-8 production in human oral epithelial cells upon stimulation with gingipains from Porphyromonas gingivalis
Authors: Uehara Akiko , Naito Mariko , Imamura Takahisa , Potempa Jan , Travis James , Nakayama Koji , Takada Haruhiko
Published: March 2008

Cysteine proteinases fromPorphyromonas gingivalis, or gingipains, are considered to be key virulence factors of the bacterium in relation to periodontal diseases. Incubation of human oral epithelial cells with lysine-specific gingipain (Kgp) and high-molecular-mass arginine-specific gingipain (HRgpA) resulted in a decrease in the production of interleukin (IL)-8, but not in the production of other pro-inflammatory cytokines. In contrast, arginine-specific gingipain 2 (RgpB) increased IL-8 production. RNA interference assays demonstrated that Kgp- and HRgpA-mediated downregulation and RgpB-mediated upregulation occurred through protease-activated receptor (PAR)-1 and PAR-2 signalling. Although the RgpB-mediated upregulation of IL-8 production occurred through nuclear factor-kappa B (NF-κB), the Kgp- and HRgpA-mediated downregulation was not negated in NF-κB-silenced cells. Both the haemagglutinin and the enzymic domains are required for Kgp and HRgpA to downregulate the production of IL-8 in human oral epithelial cells, and the two domains are thought to co-exist. These results suggest that gingipains preferentially suppress IL-8, resulting in attenuation of the cellular recognition of bacteria, and as a consequence, sustain chronic inflammation.
Development and evaluation of a loop-mediated isothermal amplification assay for rapid and simple detection of Campylobacter jejuni and Campylobacter coli
Authors: Yamazaki Wataru , Taguchi Masumi , Ishibashi Masanori , Kitazato Miyoshi , Nukina Masafumi , Misawa Naoaki , Inoue Kiyoshi
Published: March 2008

We developed a loop-mediated isothermal amplification (LAMP) assay for the rapid and simple detection of Campylobacter jejuni and Campylobacter coli. The assay provides a specific LAMP product for each of these two species. The assay correctly identified 65 C. jejuni and 45 C. coli strains, but not 75 non-C. jejuni/coli strains. The sensitivity of the LAMP assay for C. jejuni and C. coli in spiked human stool specimens was 5.6×103 c.f.u. g−1 (1.4 c.f.u. per test tube) and 4.8×103 c.f.u. g−1 (1.2 c.f.u. per test tube), respectively. When 90 stool specimens from patients with diarrhoea were tested by LAMP and direct plating, the LAMP results showed 81.3 % sensitivity and 96.6 % specificity compared to isolation of C. jejuni and C. coli by direct plating. Further, the LAMP assay required less than 2 h for detection of C. jejuni and C. coli in stool specimens. This LAMP assay is a rapid and simple tool for the detection of C. jejuni and C. coli and will be useful in facilitating the early diagnosis of food poisoning incidents caused by these organisms.
Invasive pneumococcal disease: epidemiology in children and adults prior to implementation of the conjugate vaccine in the Oxfordshire region, England
Authors: Foster Dona , Knox Kyle , Walker A. S. , Griffiths D. T. , Moore Hazel , Haworth Elizabeth , Peto Timothy , Brueggemann Angela B. , Crook Derrick W. ,   on behalf of the Oxford Invasive Pneumococcal Surveillance Group
Published: March 2008

A 10-year invasive pneumococcal disease (IPD) enhanced surveillance project in the Oxfordshire region of the UK between 1996 and 2005 identified a total of 2691 Streptococcus pneumoniae isolates from all ages that provided a comprehensive description of pneumococcal epidemiology. All isolates were serotyped and those from children under 5 years of age were genotyped and a matched case–control study using adults hospitalized between 1995 and 2000 was performed to estimate the effectiveness of the pneumococcal polysaccharide vaccine in the local population. Fifty-one serotypes were isolated, with different age distributions. The overall incidence of IPD was 9.2 cases per 100 000 population per annum [95 % confidence interval (CI), 8.6–9.9] and that of meningitis was 0.7 per 100 000 population per annum (95 % CI 0.5–0.9). After adjusting for age, serotype 1 was found to be less likely to be associated with meningitis versus other IPD, compared with the most common serotype 14, whereas serotype 12F was more likely to cause meningitis than other IPD. There were significant temporal changes in IPD incidence of four serotypes, with decreases in serotypes 1, 12F and 14 and increases in serotype 8. A possible novel variant (from serotype 6A to 6B) was found using multilocus sequence typing analysis. From the matched case–control study of adults, the pneumococcal polysaccharide vaccine effectiveness was estimated to be 43 % (2–68 %), which did not change significantly after adjustment for pre-existing co-morbidities. The data provide a baseline against which the impact of the pneumococcal conjugate vaccine introduced in the UK in 2006 could be measured.
Non-tuberculous mycobacterial infection of the parotid gland in an immunosuppressed adult
Authors: Gittinger F. S. , Raible A. , Kempf V. A. J.
Published: March 2008

Infections of the parotid gland with non-tuberculous mycobacteria (NTM) are rarely described. Here, we report on an infection of the parotid gland caused by Mycobacterium avium and give a literature-based overview about this entity. In the light of a global increase of mycobacterial infections, unusual manifestations have to be considered and should be included in the differential diagnosis when dealing with solid lesions of uncertain aetiology in the head and neck region.
De novo search for non-coding RNA genes in the AT-rich genome of Dictyostelium discoideum: Performance of Markov-dependent genome feature scoring
Authors: Larsson Pontus , Hinas Andrea , Ardell David H. , Kirsebom Leif A. , Virtanen Anders , Söderbom Fredrik
Published: March 2008

Genome data are increasingly important in the computational identification of novel regulatory non-coding RNAs (ncRNAs). However, most ncRNA gene-finders are either specialized to well-characterized ncRNA gene families or require comparisons of closely related genomes. We developed a method for de novo screening for ncRNA genes with a nucleotide composition that stands out against the background genome based on a partial sum process. We compared the performance when assuming independent and first-order Markov-dependent nucleotides, respectively, and used Karlin-Altschul and Karlin-Dembo statistics to evaluate the significance of hits. We hypothesized that a first-order Markov-dependent process might have better power to detect ncRNA genes since nearest-neighbor models have been shown to be successful in predicting RNA structures. A model based on a first-order partial sum process (analyzing overlapping dinucleotides) had better sensitivity and specificity than a zeroth-order model when applied to the AT-rich genome of the amoeba Dictyostelium discoideum. In this genome, we detected 94% of previously known ncRNA genes (at this sensitivity, the false positive rate was estimated to be 25% in a simulated background). The predictions were further refined by clustering candidate genes according to sequence similarity and/or searching for an ncRNA-associated upstream element. We experimentally verified six out of 10 tested ncRNA gene predictions. We conclude that higher-order models, in combination with other information, are useful for identification of novel ncRNA gene families in single-genome analysis of D. discoideum. Our generalizable approach extends the range of genomic data that can be searched for novel ncRNA genes using well-grounded statistical methods.
Transferrin Uptake by Rabbit Alveolar Macrophages in Vitro
Authors: WYLLIE J. C.
Published: March 2008

Summary. Rabit alveolar macrophages were shown to bind 125I‐human transferrin in vitro. The binding reaction was characterized by three stages: (I) adsorption of transferrin to the cells, followed by (2) rapid uptake of the protein to reach (3) a constant level of cell‐bound transferrin. The latter two stages were dependent upon temperature and metabolic energy. Macrophages released 125I‐transferrin rapidly when incubated with unlabelled transferrin. Small quantities of 125I‐rabbit and 125‐bovine serum albumin, by comparison, were bound to and released by the cells; the attachment of these proteins may be solely the result of adsorption. Transferrin, 80% saturated with iron, was bound to a greater extent than 10 or 50% saturated transferrin; 10% saturated transferrin was bound more readily than the 50% saturated preparation. The findings are consistent with the presence of a transferrin receptor on the cell membrane of the alveolar macrophage and imply that transferrin may interact directly with this cell type in order to remove or donate iron.
Home Treatment of Haemophilia and Christmas Disease: Five Years' Experience
Authors: Rizza C. R. , Spooner Rosemary J. D.
Published: March 2008

Summary. The Oxford home treatment programme began in 1971. The material used was human factor VIII concentrate made by the Lister Institute's Plasma Fractionation Laboratory at Oxford Haemophilia Centre. The first group of patients admitted to the programme were those making heaviest demands on the Centre for ‘on demand’ treatment. No problems were encountered by these patients, and other patients have been admitted to the programme each year since. By the end of 1975, 56 haemophilic patients and seven Christmas disease patients were receiving regular home treatment. The haemophilic patients on home treatment have on average increased their factor VIII requirements while on home treatment by 31 % to 1945 u of factor VIII per month, although some of the patients who were making very heavy demands for treatment are now using less than before starting home treatment. Since the introduction of home treatment programme, 68% of the treatment received by the 56 haemophilic patients in the scheme was given at home thus saving the patients the cost and discomfort of travelling to the Centre to receive treatment, and saving the staff of the Centre the work of giving the treatment. Including factor VIII used to cover surgical procedures and doses received at other hospitals, the patients received on average 1893 u of factor VIH per month after commencing home treatment. The standard home treatment dose received by the haemophilic patients during 1975 was 250 International Units of factor VIII which proved satisfactory in resolving the majority of bleeds. The lesions treated at home required on average 1.16 doses per bleed (290 u of factor VIII).

The Christmas disease patients receive human factor IX concentrate made by the Plasma Fractionation Laboratory in Oxford and follow a regime of weekly or fortnightly prophylactic infusions of 800–1600 u of factor IX, depending on the weight of the patient. Prophylactic infusions account for 40% of the home treatment doses received by the Christmas disease patients.
Heterogeneity of von Willebrand's disease: Study of 40 Iranian Cases
Authors: Shoa'i Irandokht , Lavergne J. M. , Ardaillou Nicole , Obert Bernadette , Ala F. , Meyer Dominique
Published: March 2008

Summary. Forty Iranian patients with von Willebrand's disease were tested for bleeding time, platelet retention to glass beads, ristocetin‐induced platelet aggregation, and assay of factor VIII procoagulant activity (VIII:C), Willebrand factor activity (VIIIRrWF), and factor VIH‐related antigen (VIIIR:AG) by two methods (Laurell and immunoradiometric assay). In 22 cases from 11 families, levels of VIII:C, VIIIR:WF and VIIIR:AG (Laurell) were below 5% and the immunoradiometric assay showed total lack of VIIIR:AG in all cases (sensitivity of the method 0.01%). In 10 of these families, the parents were related, raising the possibility that these patients are homozygous. The occurrence of precipitating antibodies to factor VIII was demonstrated in one of these severe patients. In seven cases from five families the anomaly was less severe, with results of VIII:C between 5 and 17%. In 11 cases from six families VIII:C was normal or moderately decreased, contrasting with lower levels of VIIIR:WF and VIHR:AG. The presence of an abnormal factor VHI/von Willebrand factor protein was assessed by double‐cross immunoelectro‐phoresis and gel filtration.
Monosomy 7 in Two Patients with a Myeloproliferative Disorder
Authors: Boetius G. , Hustinx T. W. J. , Smits A. P. T. , Scheres M.J. C. , Rutten F.J. , Haanen C.
Published: March 2008

Summary. Clinical and laboratory data are presented for two patients with a dyshaematopoietic disorder, and monosomy 7 in their bone marrow cells. The first patient, a 55–year‐old woman, had been treated with chlorambucil for an ovarian carcinoma. After 4 years an oligoblastic myeloid leukaemia was diagnosed and she later died with an acute transformation of the disease. The second patient, a 21–year‐old male, has had a dyserythropoietic anaemia with transient pancytopenia for over 5 years without any signs of malignancy.

The possible relationship between therapy, the monosomy 7 and the other bone marrow abnormalities is briefly discussed. From an analysis of the data of these and comparable cases in the literature it appears that loss of chromosome No. 7 material is often associated with erythropoietic disorders such as erythroid hyperplasia and erythraemia. The reduction or absence of the Colton blood group antigens found in our patients and in a few other monosomy 7 cases also points to an abnormality of the red cell line.
Changes in the Activities of some Membrane‐associated Enzymes during in Vivo Ageing of the Normal Human Erythrocyte
Authors: Kadlubowski M. , Agutter P. S.
Published: March 2008

Summary. Human erythrocytes from healthy male donors were fractionated with respect to in vivo age by simple centrifugation in order to characterize changes in the functional integrity of the membrane during the life‐span of the cell. The three enzymes, Na/K‐ATPase, glyceraldehyde‐3‐phosphate dehydrogenase and NADH‐ferricyanide reductase, were found not to change with age, but significant age‐dependent decreases were observed in the cases of acetylcholinesterase, phosphoglycerate kinase, purine nucleoside phosphorylase, adenylate kinase, Mg‐ATPase and alkaline phosphatase.

The possibility mat these changes were attributable to mechanisms other than age‐related inactivation, such as reticulocyte contamination, differential resealing and crypticity, was investigated. Only the decrease in acetylcholinesterase could be explained wholly in terms of reticulocyte contamination. A decrease in membrane integrity on ageing was observed, which accounted for approximately half the change in alkaline phosphatase and may have contributed to the other enzyme activity changes. This membrane integrity effect masked a real decrease in the highly cryptic NADH‐ferricyanide reductase, this decrease being apparent only after total disaggregation of the membrane with nonionic surfactant.
Normal Human Bone Marrow Cultures in Vitro: Cellular Composition and Maturation of the Granulocytic Colonies
Authors: Dao C. , Metcalf D. , Zittoun R. , Bilski‐Pasquier G.
Published: March 2008

Summary. The analysis of single haemopoietic colonies grown in methylcellulose and in agar was performed at intervals by a cytocentrifugation method. Correlation was established between morphology of the whole colonies and their cellular content. Three main cell lines predominated: neutrophils, macrophages, eosinophils; a few colonies contained a pure population of basophil‐like granulocytes. Development was followed from myeloblasts to polymorphs, both being present in most of the colonies. Cumulated results showed that (1) the proliferating compartment remained quite large till day 14, with 58% of cells in S phase, and rapidly decreased after day 16, and that (2) the polymorphs rapidly disappeared from the culture medium.

Differentiation proceeded at different rates from one colony to the other, thus suggesting heterogeneity between colony forming cells (CFC). Neutrophil colonies appeared and lysed more rapidly than did eosinophil colonies. Macrophages arose from large immature cells with many promyelocyte features; such cells were present in mixed colonies, containing both neutrophils and macrophages. It is very likely that granulopoiesis results from the development of distinct committed CFC.

This work was carried out using normal human bone marrow and may be a useful tool for studying pathological material in the future.
Iron Stores in Pregnancy
Authors: Fenton V. , Cavill I. , Fisher J.
Published: March 2008

Summary. Serum ferritin concentration has been measured during the course of pregnancy in 154 women. There was a rapid decrease in iron stores during early pregnancy irrespective of any iron therapy. Oral iron did, however, prevent the stores reaching iron deficient levels during the second half of pregnancy. The results suggest that maternal erythroid activity starts early in pregnancy and may exhaust the iron stores before the fetal demands for iron can be met.
INTERMITTENT TREATMENT WITH HUMAN GROWTH HORMONE (GH) IN ISOLATED GH DEFICIENCY AND IN MULTIPLE PITUITARY HORMONE DEFICIENCIES
Authors: PERTZELAN A. , KAULI R. , ASSA S. , GREENBERG D. , LARON Z.
Published: March 2008

The results of intermittent GH treatment of 3‐7½ years duration in seven patients with isolated GH deficiency (IGHD) and five patients with multiple pituitary hormone deficiencies (MPHD) are presented.

This therapeutic schedule was found to be comparably effective to those using a continuous‐administration schedule. In contradistinction to the findings obtained with the latter, there was no progressive decline in growth velocity. The patients with IGHD were found to respond better than the patients with MPHD both in the first course as well as in consequent courses. In the intervals between courses, the growth velocity was less than in the pretreatment period in both groups.

It is concluded that optimal results can be obtained by instituting an initial course of continuous treatment of 1 year's duration for the IGHD patients and of 2 years' duration for the MPHD patients, followed by an intermittent therapeutic schedule. This regime not only leads to the same growth achievement obtained with long‐term continuous administration of GH but allows conservation of supplies of this very scarce hormone.
HUMAN PITUITARY GONADOTROPHIN INDEX
Authors: BOHNET H. G. , DAHLÉN H. G. , KELLER E. , FRIEDRICH E. , SCHINDLER A. E. , WYSS H. I. , SCHNEIDER H. P. G.
Published: March 2008

To monitor the effect of LHRH treatment on hypothalamo‐pituitary‐gonadal function, women with functional amenorrhoea were investigated by standardized LHRH and repeated clomiphene tests before and after LHRH therapy. The actual pituitary gonadotrophin reserve was defined by Human Pituitary Gonadotrophin Index (HPGI). Clomiphene response served as hypothalamic function test, plasma oestradiol and progesterone concentrations were measured for assessement of the gonadal function.

LHRH treatment as performed in this study did not change basal gonadotrophin levels or the pituitary responsiveness in our standardized LHRH test. Plasma oestradiol concentrations remained unaltered at the lower limit of the early follicular phase values of a normal menstrual cycle. The inability to respond to clomiphene was changed to clomiphene responsiveness during therapy in eighteen out of twenty‐nine women with anovulation. The majority of the responders had HPG‐Indices of R 2. Patients with hyperprolactinaemic anovulation did not convert. The possibility of an ultrashort feedback action of LHRH on its own production in the human is discussed.
PROLACTIN CONCENTRATIONS IN PATIENTS WITH ACROMEGALY: CLINICAL SIGNIFICANCE AND RESPONSE TO SURGERY
Authors: FRANKS S. , JACOBS H. S. , NABARRO J. D. N.
Published: March 2008

Basal serum prolactin and growth hormone (GH) concentrations were measured by radioimmunoassay in forty patients with acromegaly. GH concentrations were elevated in all patients studied before treatment and prolactin levels were raised in seven of twenty‐six patients. Of the thirty‐two patients reviewed after treatment which in most cases was transsphenoidal hypophysectomy) twenty‐five had GH concentrations below 5 ng/ml and twenty‐nine had normal prolactin levels. In eighteen patients hormone measurements were made both before and after hypophysectomy: though GH levels fell in but one, prolactin fell in only six patients. They were not significantly changed in eleven patients. There was no correlation of GH and prolactin either before or after surgery.

Seven patients had greatly elevated prolactin levels and in four of these there was evidence of upward extension of a pituitary tumour on air encephalogram (AEG). Only one patient with a normal prolactin level had an abnormal AEG. Two patients with elevated prolactin concentrations and normal AEGs had a parallel fall of prolactin and GH in response to surgery. Four of the five hyperprolactinaemic men complained of loss of libido: in three gonadotrophin concentrations before and after treatment were normal.

We conclude that there is no overall correlation of GH and prolactin levels in patients with acromegaly. Seven of twenty‐six untreated patients (27%) had hyperprolactinaemia. We suggest that in these patients a raised prolactin level may be due either to interference with the normal inbhitory control mechanism of prolactin by suprasellar extension or, more rarely, to secretion of both GH and prolactin by the tumour itself. A high prolactin concentration may be the cause of the impotence of which some patients with acromegaly complain.
THE ADRENOCORTICAL STATUS OF PATIENTS WITH THYROID DISEASE
Authors: BRIEN T. G.
Published: March 2008

Summary. Plasma cortisol, cortisol resin uptake ratio and free cortisol index was measured in twenty‐seven euthyroid, ten hypothyroid and fifteen hyperthyroid subjects. No difference was observed between euthyroid subjects and patients with thyroid disease for any of the three parameters tested. The significance of these findings is discussed in the light of earlier reports linking thyroid activity with the levels of corticosteroid binding globulin.
A RE‐EXAMINATION OF THE CONFORMATION OF SECRETIN IN WATER
Authors: BODANSZKY MIKLOS , FINK MARY LYNN , FUNK KENNETH W. , SAID SAMI I.
Published: March 2008

An examination of a series of peptides corresponding to partial sequences of secretin and the application of empirical conformational parameters to the sequence has reopened the question about the position of the short helical stretch in the folded chain. In earlier studies, this was tentatively placed near the Nterminus, while newly accumulated evidence points to the C‐terminal area.

The possible role of ion paris in the stabilization of the folding was investigated by the preparation and examination of synthetic analogues of the C‐terminal tricosapeptide part of secretin. The carboxy grups of glutamic acid (in position 9) and of aspartic acid (in position 15) were replaced by carboxamides. The 9‐glutamine and the 15‐asparagine analogues show a signifcant decrease in helical character. This loss of 'structure’is even more pronounced in the 9‐glutamine‐15‐asparagine tricospetide. Thus, ion ‐pair formation is indeed implicated as one of the forces which stabilize the folded conformation of the chain. Possible corelations between biological activity and secretin‐like architecture were studied on severl smooth muscle preparations.