bluuebunny/crossref_metadata_2025 huggingface dataset:
Using contextual and lexical features to restructure and validate the classification of biomedical concepts
Authors: Fan Jung-Wei , Xu Hua , Friedman Carol
Published: July 2007

Background

Biomedical ontologies are critical for integration of data from diverse sources and for use by knowledge-based biomedical applications, especially natural language processing as well as associated mining and reasoning systems. The effectiveness of these systems is heavily dependent on the quality of the ontological terms and their classifications. To assist in developing and maintaining the ontologies objectively, we propose automatic approaches to classify and/or validate their semantic categories. In previous work, we developed an approach using contextual syntactic features obtained from a large domain corpus to reclassify and validate concepts of the Unified Medical Language System (UMLS), a comprehensive resource of biomedical terminology. In this paper, we introduce another classification approach based on words of the concept strings and compare it to the contextual syntactic approach.

Results

The string-based approach achieved an error rate of 0.143, with a mean reciprocal rank of 0.907. The context-based and string-based approaches were found to be complementary, and the error rate was reduced further by applying a linear combination of the two classifiers. The advantage of combining the two approaches was especially manifested on test data with sufficient contextual features, achieving the lowest error rate of 0.055 and a mean reciprocal rank of 0.969.

Conclusion

The lexical features provide another semantic dimension in addition to syntactic contextual features that support the classification of ontological concepts. The classification errors of each dimension can be further reduced through appropriate combination of the complementary classifiers.
BPhyOG: An interactive server for genome-wide inference of bacterial phylogenies based on overlapping genes
Authors: Luo Yingqin , Fu Cong , Zhang Da-Yong , Lin Kui
Published: July 2007

Background

Overlapping genes (OGs) in bacterial genomes are pairs of adjacent genes of which the coding sequences overlap partly or entirely. With the rapid accumulation of sequence data, many OGs in bacterial genomes have now been identified. Indeed, these might prove a consistent feature across all microbial genomes. Our previous work suggests that OGs can be considered as robust markers at the whole genome level for the construction of phylogenies. An online, interactive web server for inferring phylogenies is needed for biologists to analyze phylogenetic relationships among a set of bacterial genomes of interest.

Description

BPhyOG is an online interactive server for reconstructing the phylogenies of completely sequenced bacterial genomes on the basis of their shared overlapping genes. It provides two tree-reconstruction methods: Neighbor Joining (NJ) and Unweighted Pair-Group Method using Arithmetic averages (UPGMA). Users can apply the desired method to generate phylogenetic trees, which are based on an evolutionary distance matrix for the selected genomes. The distance between two genomes is defined by the normalized number of their shared OG pairs. BPhyOG also allows users to browse the OGs that were used to infer the phylogenetic relationships. It provides detailed annotation for each OG pair and the features of the component genes through hyperlinks. Users can also retrieve each of the homologous OG pairs that have been determined among 177 genomes. It is a useful tool for analyzing the tree of life and overlapping genes from a genomic standpoint.

Conclusion

BPhyOG is a useful interactive web server for genome-wide inference of any potential evolutionary relationship among the genomes selected by users. It currently includes 177 completely sequenced bacterial genomes containing 79,855 OG pairs, the annotation and homologous OG pairs of which are integrated comprehensively. The reliability of phylogenies complemented by annotations make BPhyOG a powerful web server for genomic and genetic studies. It is freely available athttp://cmb.bnu.edu.cn/BPhyOG.
Knowledge and attitudes of parents and professionals to neonatal BCG vaccination in light of recent UK policy changes: A questionnaire study
Authors: Gordon Morris , Roberts Hannah , Odeka Egware
Published: July 2007

Background

Universal BCG vaccination in the UK ended in 2005. The new vaccination policy instead offers a number of different forms of selective vaccination to newborns based on risk of acquiring TB. We set out to assess the attitudes and knowledge of both parents and professionals to the new policy for neonatal BCG vaccination.

Methods

A short questionnaire was designed, made up of demographic and attitude questions, as well as very basic knowledge questions. The researchers handed out the questionnaire to all parents and professionals in the antenatal and postnatal areas, as well as the paediatric and neonatal units during a 6-week period. The site was the Royal Oldham hospital, a district general hospital with 3250 deliveries per year and multi-ethnic in its population mix.

Results

A total of 253 completed questionnaires were collected. The ethnic origin of responders was 50.6% White British, 18.2% Bangladeshi, 8.7% Indian, 4% White/Asian, the remaining 18.5% of other origins. 71.5% of responders said they had heard of BCG vaccine. When asked if they knew the new policy for its use, 33.2% answered yes. 24.5% gave the most accurate response when asked who now receives BCG.

Conclusion

We have found that amongst parents and professionals alike there is a lack of knowledge of the new policy. This has lead to confusion and as knowledge amongst the professionals who identify neonates for vaccination is low, uptake may be sub-optimal. We suggest that units investigate the issue and ensure that the new policy is understood and implemented correctly.
Unilateral congenital elongation of the cervical part of the internal carotid artery with kinking and looping: two case reports and review of the literature
Authors: Ovchinnikov Nikolai A , Rao Ramesh T , Rao Suresh R
Published: July 2007

Unilateral and bilateral variation in the course and elongation of the cervical (extracranial) part of the internal carotid artery (ICA) leading to its tortuosity, kinking and coiling or looping is not a rare condition, which could be caused by both embryological and acquired factors. Patients with such variations may be asymptomatic in some cases; in others, they can develop cerebrovascular symptoms due to carotid stenosis affecting cerebral circulation. The risk of transient ischemic attacks in patients with carotid stenosis is high and its surgical correction is indicated for the prevention of ischemic stroke. Detection of developmental variations of the ICA and evaluation of its stenotic areas is very important for surgical interventions and involves specific diagnostic imaging techniques for vascular lesions including contrast arteriography, duplex ultrasonography and magnetic resonance angiography. Examination of obtained images in cases of unusual and complicated variations of vascular pattern of the ICA may lead to confusion in interpretation of data. Awareness about details and topographic anatomy of variations of the ICA may serve as a useful guide for both radiologists and vascular surgeons. It may help to prevent diagnostic errors, influence surgical tactics and interventional procedures and avoid complications during the head and neck surgery. Our present study was conducted with a purpose of updating data about developmental variations of the ICA. Dissections of the main neurovascular bundle of the head and neck were performed on a total 14 human adult cadavers (10 – Africans: 7 males & 3 females and 4 – East Indians: all males). Two cases of unilateral congenital elongation of the cervical part of the ICA with kinking and looping and carotid stenoses were found only in African males. Here we present their detailed case reports with review of the literature.
Nonlinear regulation enhances the phenotypic expression of trans- acting genetic polymorphisms
Authors: Gjuvsland Arne B , Hayes Ben J , Meuwissen Theo HE , Plahte Erik , Omholt Stig W
Published: July 2007

Background

Genetic variation explains a considerable part of observed phenotypic variation in gene expression networks. This variation has been shown to be located both locally (cis) and distally (trans) to the genes being measured. Here we explore to which degree the phenotypic manifestation of local and distant polymorphisms is a dynamic feature of regulatory design.

Results

By combining mathematical models of gene expression networks with genetic maps and linkage analysis we find that very different network structures and regulatory motifs give similar cis/trans linkage patterns. However, when the shape of the cis- regulatory input functions is more nonlinear or threshold-like, we observe for all networks a dramatic increase in the phenotypic expression of distant compared to local polymorphisms under otherwise equal conditions.

Conclusion

Our findings indicate that genetic variation affecting the form of cis-regulatory input functions may reshape the genotype-phenotype map by changing the relative importance of cis and trans variation. Our approach combining nonlinear dynamic models with statistical genetics opens up for a systematic investigation of how functional genetic variation is translated into phenotypic variation under various systemic conditions.
Patients with Mutations in Gsα Have Reduced Activation of a Downstream Target in Epithelial Tissues due to Haploinsufficiency
Authors: Hsu Stephanie C. , Groman Joshua D. , Merlo Christian A. , Naughton Kathleen , Zeitlin Pamela L. , Germain-Lee Emily L. , Boyle Michael P. , Cutting Garry R.
Published: July 2007

Context: Patients with Albright hereditary osteodystrophy (AHO) have defects in stimulatory G protein signaling due to loss of function mutations in GNAS. The mechanism by which these mutations lead to the AHO phenotype has been difficult to establish due to the inaccessibility of the affected tissues.

Objective: The objective of the study was to gain insight into the downstream consequences of abnormal stimulatory G protein signaling in human epithelial tissues.

Patients and Design: We assessed transcription of GNAS and Gsα-stimulated activation of the cystic fibrosis transmembrane conductance regulator (CFTR) in AHO patients, compared with normal controls and patients with cystic fibrosis.

Main Outcome Measures: Relative expression of Gsα transcripts from each parental GNAS allele and cAMP measurements from nasal epithelial cells were compared among normal controls and AHO patients. In vivo measurements of CFTR function, pulmonary function, and pancreatic function were assessed in AHO patients.

Results: GNAS was expressed equally from each allele in normals and two of five AHO patients. cAMP generation was significantly reduced in nasal respiratory epithelial cells from AHO patients, compared with normal controls (0.4 vs. 0.6, P = 0.0008). Activation of CFTR in vivo in nasal (P = 0.0065) and sweat gland epithelia (P = 0.01) of AHO patients was significantly reduced from normal. In three patients, the reduction in activity was comparable with patients with cystic fibrosis due to mutations in CFTR. Yet no AHO patients had pulmonary or pancreatic disease consistent with cystic fibrosis.

Conclusions: In humans, haploinsufficiency of GNAS causes a significant reduction in the activation of the downstream target, CFTR, in vivo.
Succinate Dehydrogenase B Gene Mutations Predict Survival in Patients with Malignant Pheochromocytomas or Paragangliomas
Authors: Amar Laurence , Baudin Eric , Burnichon Nelly , Peyrard Séverine , Silvera Stéphane , Bertherat Jérôme , Bertagna Xavier , Schlumberger Martin , Jeunemaitre Xavier , Gimenez-Roqueplo Anne-Paule , Plouin Pierre-François
Published: July 2007

Context: Pheochromocytomas and paragangliomas may be malignant either at presentation or during recurrence, but the clinical course of malignant tumors is unpredictable.

Objective: The objective was to analyze survival according to clinical characteristics at diagnosis of malignancy and the presence or absence of SDHB mutations.

Design: This was a retrospective cohort study.

Setting and Participants: A total of 54 patients with malignant tumors were included. Malignancy was scored according to the presence of metastases or histologically documented lymph node invasion.

Main Outcome Measures: The main outcome was the specific survival after the diagnosis of the first metastasis.

Results: Germline mutations were identified in SDHB (n = 23, including 21 patients with apparent sporadic tumors) and VHL (n = 1) genes, and two patients had neurofibromatosis 1. Patients were followed up from the diagnosis of primary tumor and from the diagnosis of the first metastasis to the present or to death with medians of 79 [interquartile range (IQR) 24; 190] and 39 [IQR 14; 94] months, respectively. The 5-yr probability of survival after the diagnosis of the first metastasis was 0.55 (95% confidence interval 0.39–0.69). Patients with SDHB mutations were younger, more frequently had extra-adrenal tumors, and had a shorter metanephrine excretion doubling time. The presence of SDHB mutations was significantly and independently associated with mortality (relative risk 2.7; 95% confidence interval 1.2, 6.4; P = 0.021).

Conclusion: SDHB mutations, frequent in patients with malignant pheochromocytomas or paragangliomas, are associated with shorter survival. Therefore, SDHB genetic testing may be of prognostic value for such patients, even those with an apparent sporadic and/or benign presentation at diagnosis.
Overexpression of Micro Ribonucleic Acid 29, Highly Up-Regulated in Diabetic Rats, Leads to Insulin Resistance in 3T3-L1 Adipocytes
Authors: He Aibin , Zhu Liuluan , Gupta Nishith , Chang Yongsheng , Fang Fude
Published: July 2007

Micro-RNAs (miRNAs) have been suggested to play pivotal roles in multifarious diseases associated with the posttranscriptional regulation of protein-coding genes. In this study, we aimed to investigate the function of miRNAs in type 2 diabetes mellitus. The miRNAs expression profiles were examined by miRNA microarray analysis of skeletal muscles from healthy and Goto-Kakizaki rats. We identified four up-regulated miRNAs, and 11 miRNAs that were down-regulated relative to normal individuals. Among induced miRNAs were three paralogs of miR-29, miR-29a, miR-29b, and miR-29c. Northern blotting further confirmed their elevated expression in three important target tissues of insulin action: muscle, fat, and liver of diabetic rats. Adenovirus-mediated overexpression of miR-29a/b/c in 3T3-L1 adipocytes could largely repress insulin-stimulated glucose uptake, presumably through inhibiting Akt activation. The increase in miR-29 level caused insulin resistance, similar to that of incubation with high glucose and insulin in combination, which, in turn, induced miR-29a and miR-29b expression. In this paper, we demonstrate that Akt is not the direct target gene of miR-29 and that the negative effects of miR-29 on insulin signaling might be mediated by other unknown intermediates. Taken together, these data reveal the crucial role of miR-29 in type 2 diabetes.
Lipoamide dehydrogenase mediates retention of coronin-1 on BCG vacuoles, leading to arrest in phagosome maturation
Authors: Deghmane Ala-Eddine , Soualhine Hafid , Bach Horacio , Sendide Khalid , Itoh Saotomo , Tam Andrea , Noubir Sanaa , Talal Amina , Lo Raymond , Toyoshima Satoshi , Av-Gay Yossef , Hmama Zakaria
Published: July 2007

Mycobacterium tuberculosis evades the innate antimicrobial defenses of macrophages by inhibiting the maturation of its phagosome to a bactericidal phagolysosome. Despite intense studies of the mycobacterial phagosome, the mechanism of mycobacterial persistence dependent on prolonged phagosomal retention of the coat protein coronin-1 is still unclear. The present study demonstrated that several mycobacterial proteins traffic intracellularly in M. bovis BCG-infected cells and that one of them, with an apparent subunit size of Mr 50,000, actively retains coronin-1 on the phagosomal membrane. This protein was initially termed coronin-interacting protein (CIP)50 and was shown to be also expressed by M. tuberculosis but not by the non-pathogenic species M. smegmatis. Cell-free system experiments using a GST-coronin-1 construct showed that binding of CIP50 to coronin-1 required cholesterol. Thereafter, mass spectrometry sequencing identified mycobacterial lipoamide dehydrogenase C (LpdC) as a coronin-1 binding protein. M. smegmatis over-expressing Mtb LpdC protein acquired the capacity to maintain coronin-1 on the phagosomal membrane and this prolonged its survival within the macrophage. Importantly, IFNγ-induced phagolysosome fusion in cells infected with BCG resulted in the dissociation of the LpdC-coronin-1 complex by a mechanism dependent, at least in part, on IFNγ-induced LRG-47 expression. These findings provide further support for the relevance of the LpdC-coronin-1 interaction in phagosome maturation arrest.
Mapping ErbB receptors on breast cancer cell membranes during signal transduction
Authors: Yang Shujie , Raymond-Stintz Mary Ann , Ying Wenxia , Zhang Jun , Lidke Diane S. , Steinberg Stanly L. , Williams Lance , Oliver Janet M. , Wilson Bridget S.
Published: July 2007

Distributions of ErbB receptors on membranes of SKBR3 breast cancer cells were mapped by immunoelectron microscopy. The most abundant receptor, ErbB2, is phosphorylated, clustered and active. Kinase inhibitors ablate ErbB2 phosphorylation without dispersing clusters. Modest co-clustering of ErbB2 and EGFR, even after EGF treatment, suggests that both are predominantly involved in homointeractions. Heregulin leads to dramatic clusters of ErbB3 that contain some ErbB2 and EGFR and abundant PI 3-kinase. Other docking proteins, such as Shc and STAT5, respond differently to receptor activation. Levels of Shc at the membrane increase two- to five-fold with EGF, whereas pre-associated STAT5 becomes strongly phosphorylated. These data suggest that the distinct topography of receptors and their docking partners modulates signaling activities.
Clonal analysis of nestin– vimentin+ multipotent fibroblasts isolated from human dermis
Authors: Chen Fu Guo , Zhang Wen Jie , Bi Dan , Liu Wei , Wei Xian , Chen Fan Fan , Zhu Lian , Cui Lei , Cao Yilin
Published: July 2007

Although several studies have shown that dermal fibroblasts possess adipogenic, osteogenic or chondrogenic differentiation potential, no study has characterized this cell population in detail, and there is as yet no evidence that a single dermal fibroblast can differentiate into all these types of cells. In this study, dermal fibroblasts were isolated from human foreskin using a regular dermal fibroblast culture system. These cells could be expended in adherent culture for over 40 cell doublings. In addition, dermal fibroblasts exhibited adipogenic, osteogenic and chondrogenic phenotypes when they were cultured in the presence of certain inducers. Importantly, clonal analysis showed that 6.4% (3/47) of the single-cell-derived clones were tripotent, 19.1% (9/47) of the clones were bipotent, and 10.6% (5/47) of the clones were unipotent. Furthermore, one of the three tested tripotent clones exhibited neurogenic and hepatogenic differentiation potential. Phenotypic analyses showed that the tripotent fibroblasts were nestin– vimentin+, which is different from the dermis-derived stem cells reported by others. These results indicate that dermal fibroblasts are a heterogeneous population containing progenitors with various levels of differentiation potential, and the nestin– vimentin+ fibroblasts may represent a novel type of multipotent adult stem cells in human dermis.
Quantitative studies of lymphoid organs, blood and lymph in inbred athymic and euthymic LEW rats under germfree and specified-pathogen-free conditions
Authors: Klausen B. , Hougen H. P.
Published: July 2007

Four groups of inbred male LEW rats were examined: A, germfree athymic; B, specified pathogen free (SPF) athymic; C, germfree euthymic; D, SPF euthymic. All animals were killed at 18 weeks and compared with respect to body weight, histological appearance and cell density of the lymphoid organs, haematological values and differential counts of bone marrow, peripheral blood and lymph.

Athymic rats had a lower body weight, less densely populated lymphoid organs, and fewer lymphocytes in the blood and lymph compared with euthymic animals. No difference was seen between athymic rats under germfree and SPF conditions, and in general the differences between athymic and euthymic animals were less pronounced under germfree conditions.
Serodiagnosis of cilia-associated respiratory bacillus infection by the indirect immunofluorescence assay technique
Authors: Matsushita S. , Kashima M. , Joshima H.
Published: July 2007

Antibody to cilia-associated respiratory (CAR) bacillus was detected by the indirect immunofluorescence assay (IFA) technique using tracheal sections of infected mice as antigen in serum samples collected from rats infected naturally and experimentally. Nine of 23 cases of natural infection were positive in IFA antibody, with titres ranging from 1:10 to 1:80, and all these antibody-positive cases were also histologically positive. The remaining 14 cases were negative in both IFA antibody and histological diagnosis, even though some of them were infected with Sendai virus and Mycoplasma pulmonis. In the experimental infection, serum samples collected from 18 rats on days 4, 7, 14, 21, 28 and 56 post-inoculation (PI) (three rats for each point) and examined for IFA antibody revealed that seroconversion occurred in one rat on day 14 PI and in three rats on day 21 PI. Antibody titres of 1:80 to 1:160 remained to the termination of the experiment. The IFA technique was useful for the diagnosis of CAR bacillus infection except in the early stage of the infection.
Acute diarrhoeal disease in rabbit: bacteriological diagnosis and efficacy of oral rehydration in combination with loperamide hydrochloride
Authors: Banerjee A. K. , Angulo A. F. , Dhasmana K. M. , Kong-A-San J.
Published: July 2007

Acute outbreaks of diarrhoea with high mortality rates are frequently observed in rabbits. Amongst various aetiological factors Escherichia coli or its toxins have been found to be commonly incriminated. Sulphonamides or antibiotics are used to treat rabbits with bacterial diarrhoea. The result of the antibiotic treatment is moderately successful. We had good results using oral rehydration treatment in combination with loperamide hydrochloride (Immodium®) in a colony of rabbits with E. coli diarrhoea.
Does the rat have an empty stomach after an overnight fast?
Authors: Jeffrey P. , Burrows M. , Bye A.
Published: July 2007

Variable amounts of food have been observed in the stomachs of male rats following an overnight fast. The effects of diet and diet type on the amount of residual food left in the stomach and on fat deposition and liver weight in the male rat were investigated. The implications of these results on metabolism and pharmacokinetic studies are discussed.
Fluorescent labeling of tRNAs for dynamics experiments
Authors: Betteridge Thu , Liu Hanqing , Gamper Howard , Kirillov Stanislav , Cooperman Barry S. , Hou Ya-Ming
Published: July 2007

Transfer RNAs (tRNAs) are substrates for complex enzymes, such as aminoacyl-tRNA synthetases and ribosomes, and play an essential role in translation of genetic information into protein sequences. Here we describe a general method for labeling tRNAs with fluorescent dyes, so that the activities and dynamics of the labeled tRNAs can be directly monitored by fluorescence during the ribosomal decoding process. This method makes use of the previously reported fluorescent labeling of natural tRNAs at dihydrouridine (D) positions, but extends the previous method to synthetic tRNAs by preparing tRNA transcripts and introducing D residues into transcripts with the yeast enzyme Dus1p dihydrouridine synthase. Using the unmodified transcript of Escherichia coli tRNAPro as an example, which has U17 and U17a in the D loop, we show that Dus1p catalyzes conversion of one of these Us (mostly U17a) to D, and that the modified tRNA can be labeled with the fluorophores proflavin and rhodamine 110, with overall labeling yields comparable to those obtained with the native yeast tRNAPhe. Further, the transcript of yeast tRNAPhe, modified by Dus1p and labeled with proflavin, translocates on the ribosome at a rate similar to that of the proflavin-labeled native yeast tRNAPhe. These results demonstrate that synthetic tRNA transcripts, which may be designed to contain mutations not found in nature, can be labeled and studied. Such labeled tRNAs should have broad utility in research that involves studies of tRNA maturation, aminoacylation, and tRNA–ribosome interactions.
VICKZ proteins mediate cell migration via their RNA binding activity
Authors: Oberman Froma , Rand Kinneret , Maizels Yael , Rubinstein Ariel M. , Yisraeli Joel K.
Published: July 2007

The highly conserved, RNA binding VICKZ proteins help regulate RNA localization, stability, and translation in many eukaryotes. These proteins are also required for cell migration in embryos and cultured cells. In adults, many tumors overexpress VICKZ homologs, and it has been hypothesized that the proteins can mediate cell motility and invasion. How these proteins facilitate cell movement and, in particular, whether their ability to bind RNA plays a role in their function remain unclear. Using HPLC and mass spectrometry to identify a region of Xenopus Vg1 RBP (xVICKZ3) that binds the vegetal localization element of Vg1 RNA, we generated a deletion construct that functions in a dominant-negative manner. The construct associates with full-length xVICKZ3 and severely reduces binding to target RNAs. This dominant-negative construct phenocopies the effect of down-regulating xVICKZ3 in Xenopus embryos. A corresponding deletion in the human homolog hVICKZ1 similarly functions in a dominant-negative fashion to reduce the ability of full-length hVICKZ protein to bind RNA. Expression of the dominant-negative construct in human carcinoma cells inhibits cell movement by several criteria. We conclude that the ability of VICKZ proteins to mediate cell migration, in vitro and in vivo, requires their RNA binding activity.
Mg2+ binding and archaeosine modification stabilize the G15–C48 Levitt base pair in tRNAs
Authors: Oliva Romina , Tramontano Anna , Cavallo Luigi
Published: July 2007

The G15–C48 Levitt base pair, located at a crucial position in the core of canonical tRNAs, assumes a reverse Watson–Crick (RWC) geometry. By means of bioinformatics analysis and quantum mechanics calculations we show here that such a geometry is moderately more stable than an alternative bifurcated trans geometry, involving the guanine Watson–Crick face and the cytosine keto group, which we have also found in known RNA structures. However we also demonstrate that the RWC geometry can take advantage of additional stabilizing effects such as metal binding or post-transcriptional chemical modification. One of the few strong metal binding sites characterized for cytosolic tRNAs is localized on G15, and a domain-specific complex modification known as archaeosine is widespread at position 15 in archaeal tRNAs. We have found that both the bound Mg2+ ion and the archaeosine modification induce an analogous electron density redistribution, which results in an effective stabilization of the RWC geometry. Metal binding and chemical modification thus play an interchangeable role in stabilizing the G15–C48 correct geometry. Interestingly, these different but convergent strategies are selectively adopted in the different life domains.
Roles of the HEAT repeat proteins Utp10 and Utp20 in 40S ribosome maturation
Authors: Dez Christophe , Dlakić Mensur , Tollervey David
Published: July 2007

A family of HEAT-repeat containing ribosome synthesis factors was previously identified in Saccharomyces cerevisiae. We report the detailed characterization of two of these factors, Utp10 and Utp20, which were initially identified as components of the small subunit processome. Coprecipitation analyses confirmed the association of Utp10 and Utp20 with U3 snoRNA and the early pre-rRNA processing intermediates. Particularly strong association was seen with aberrant processing intermediates, which may help target these RNAs for degradation. Genetic depletion of either protein inhibited the early pre-rRNA processing steps in 18S rRNA maturation but had little effect on pre-rRNA transcription or synthesis of the 25S or 5.8S rRNAs. The absence of the poly(A) polymerase Trf5, a component of the TRAMP5 complex and exosome cofactor, led to stabilization of the aberrant 23S RNA in strains depleted of Utp10 or Utp20. In the case of Utp10, 20S pre-rRNA synthesis was also modestly increased by this loss of surveillance activity.
Distinguishing species
Authors: Müller Tobias , Philippi Nicole , Dandekar Thomas , Schultz Jörg , Wolf Matthias
Published: July 2007

Given two organisms, how can one distinguish whether they belong to the same species or not? This might be straightforward for two divergent organisms, but can be extremely difficult and laborious for closely related ones. A molecular marker giving a clear distinction would therefore be of immense benefit. The internal transcribed spacer 2 (ITS2) has been widely used for low-level phylogenetic analyses. Case studies revealed that a compensatory base change (CBC) in the helix II or helix III ITS2 secondary structure between two organisms correlated with sexual incompatibility. We analyzed more than 1300 closely related species to test whether this correlation is generally applicable. In 93%, where a CBC was found between organisms classified within the same genus, they belong to different species. Thus, a CBC in an ITS2 sequence-structure alignment is a sufficient condition to distinguish even closely related species.
The mouse homolog of HEN1 is a potential methylase for Piwi-interacting RNAs
Authors: Kirino Yohei , Mourelatos Zissimos
Published: July 2007

Piwi-interacting RNAs (piRNAs) are a novel class of small regulatory RNAs that are expressed specifically and abundantly in germ cells. Mammalian piRNAs are 26–31 nucleotides in length and bind to Piwi proteins, but their function and biogenesis remain elusive. We previously showed that mammalian piRNAs are 2′-O-methylated at their 3′ termini. The biosynthetic mechanism and function of this modification is unknown. Here, we report that the mouse homolog (mHEN1) of HEN1, a plant microRNA (miRNA) 2′-O-methyltransferase, is expressed specifically in testis and methylates 3′ termini of piRNAs in vitro. These findings provide insight into the biogenesis of piRNAs.
Pharmacotherapeutic Options for Overweight Adolescents
Authors: Dunican Kaelen C , Desilets Alicia R , Montalbano Julie K
Published: July 2007

Objective:

To evaluate the safety and efficacy of current pharmacotherapeutic options for weight loss in overweight adolescents.

Data Sources:

Literature was obtained through MEDLINE Ovid (1996–April 2007) and EMBASE Drugs and Pharmacology (1991–2nd quarter 2007) searches and a bibliographic review of published articles. Key words included adolescents, overweight, obesity, anti-obesity agents, drug therapy, orlistat, sibutramine, and metformin.

Study Selection and Data Extraction:

All studies published in the English language that evaluated the use of pharmacotherapy for the treatment of overweight adolescents were critically analyzed; pertinent articles were selected for this review.

Data Synthesis:

Orlistat has been approved for use in adolescents between the ages of 12 and 16 years. The most frequently reported adverse effects of orlistat were gastrointestinal; reduced concentrations of fat-soluble vitamins were also observed. Of the 6 clinical trials published, 5 have shown statistically significant reductions in body mass index {BMI) from baseline, ranging from 0.55 to 4.09 kg/m2; one small trial failed to demonstrate significant weight reduction compared with placebo. Sibutramine has also been evaluated for use in overweight adolescents in 6 trials. Trials demonstrated a statistically significant reduction in BMI up to 5.6 kg/m2 (from baseline). Of concern is evidence indicating that sibutramine therapy may be associated with elevated blood pressure, increased pulse rate, depression, and suicidal ideations. Lastly, metformin has recently been evaluated for weight loss in overweight adolescents; small, short-term trials demonstrate modest reductions in weight and BMI.

Conclusions:

Orlistat has been proven both safe and effective for weight reduction in overweight adolescents. Sibutramine has also been proven effective in reducing weight in this population; however, the potential for severe adverse effects requires further investigation. Metformin has demonstrated promising results in small trials; its role in the treatment of overweight adolescents will remain investigational until further research is conducted.
Daptomycin Use After Vancomycin-Induced Neutropenia in a Patient with Left-Sided Endocarditis
Authors: Mergenhagen Kari A , Pasko Mary T
Published: July 2007

Objective:

To report a positive outcome in a patient treated with daptomycin for left-sided endocarditis associated with methicillin-resistant Staphylococcus aureus (MRSA) subsequent to vancomycin-induced neutropenia.

Case Summary:

A 55-year-old African American male was diagnosed with left-sided endocarditis, brain abscesses, and septic arthritis due to community-acquired MRSA. He began treatment with intravenous vancomycin to achieve a trough concentration of 15–20 μg/mL and oral rifampin 600 mg/day. A repair and resection of the mitral valve was completed on day 15 of hospitalization. Vancomycin was discontinued on day 36 secondary to drug-induced neutropenia (absolute neutrophil count nadir 162 cells/μL). Intravenous therapy with daptomycin 6 mg/kg every 24 hours was then initiated and the neutropenia resolved. The patient was discharged from the hospital on day 56.

Discussion:

Upon discontinuation of vancomycin, treatment options were limited to a small number of alternatives. Documented clinical experience and relevant studies are limited regarding the use of quinupristin/dalfopristin (Q/D), linezolid, trimethoprim/sulfamethoxazole (TMP/SMX), and daptomycin for the treatment of MRSA left-sided endocarditis. Daptomycin was selected because of its bactericidal qualities and its recent approval for this indication. The prognostic outlook for use of daptomycin in this treatment was uncertain; however, Q/D, linezolid, and TMP/SMX posed greater risks of failure.

Conclusions:

Treatment of MRSA left-sided endocarditis in patients intolerant to vancomycin is challenging. The positive outcome in our patient is likely attributable to aggressive vancomycin dosing and extended duration of treatment prior to the initiation of daptomycin. The use of daptomycin in this case enabled successful management of left-sided endocarditis.
Specific and Sensitive Immunoassays Detect Multiple Anti-ovarian Antibodies in Women With Infertility
Authors: Pires Eusebio S. , Meherji Pervin K. , Vaidya Rama R. , Parikh Firuza R. , Ghosalkar Manish N. , Khole Vrinda V.
Published: July 2007

Serum anti-ovarian antibodies (AOAs) have been shown in autoimmune premature ovarian failure and in vitro fertilization-embryo transfer (IVF-ET) cases. The specificity of assays detecting these antibodies has been questioned. Researchers have used several techniques (e.g., ELISA and indirect immunofluorescence). Few have reported on the non-specificity and the type of molecular and cellular targets. We reported earlier on the presence of naturally occurring anti-albumin antibodies as the likely factor for non-specificity. Having developed a novel blocking recipe, we show substantial elimination of this non-specificity. With these standardized tests, we hereby report multiple targets at protein and histological levels. In our study group, 15 of 50 (30%) patients with premature ovarian failure and 13 of 50 (26%) IVF-ET patients showed the presence of AOAs. Western blotting showed a large number of patients making AOAs to a 90-kDa protein, followed by 97- and 120-kDa proteins. Histochemically, it was evident that the sera of these patients predominantly react with the oocyte; other somatic cellular targets are also involved. The specific non-invasive test developed by us was found to be useful because it could carry out a reliable diagnosis of an autoimmune etiology that would be very helpful to select patients in whom immune-modulating therapy could be recommended, which in turn may restore ovarian function and fertility.
The Role of Spatial Attention in the Selection of Real and Illusory Objects
Authors: Martinez Antígona , Ramanathan Dhakshin S. , Foxe John J. , Javitt Daniel C. , Hillyard Steven A.
Published: July 2007

Selective attention may be flexibly directed toward particular locations in the visual field (spatial attention) or to entire object configurations (object-based attention). A key question is whether spatial attention plays a direct role in the selection of objects, perhaps by spreading its facilitatory influence throughout the boundaries of an object. We studied the relationship between spatial and object-based attention in a design in which subjects attended to brief offsets of one corner of a real or illusory square form. Object-selective attention was indexed by differences in event-related potential (ERP) amplitudes and blood oxygen level-dependent (BOLD) activations to unattended corner offsets in conditions in which the objects were intact versus fragmented or absent. This design ensured that object-based attention effects were not an artifact of attention being guided by simple directional cues such as parallel lines, which may have occurred in previous studies. Both space-based and object-based attention were associated with enhanced negative ERPs (N1 component at 140–180 ms) that were colocalized with BOLD activations in lateral occipital cortex (LOC). These results provide physiological evidence that directing spatial attention to one part of an object (whether real or illusory) facilitates the processing of the entire object at the level of the LOC and thus contributes directly to object-based selective attention.
Reduced Vesicular Storage of Dopamine Causes Progressive Nigrostriatal Neurodegeneration
Authors: Caudle W. Michael , Richardson Jason R. , Wang Min Z. , Taylor Tonya N. , Guillot Thomas S. , McCormack Alison L. , Colebrooke Rebecca E. , Di Monte Donato A. , Emson Piers C. , Miller Gary W.
Published: July 2007

The vesicular monoamine transporter 2 (VMAT2; SLC18A2) is responsible for packaging dopamine into vesicles for subsequent release and has been suggested to serve a neuroprotective role in the dopamine system. Here, we show that mice that express ∼5% of normal VMAT2 (VMAT2 LO) display age-associated nigrostriatal dopamine dysfunction that ultimately results in neurodegeneration. Elevated cysteinyl adducts tol-DOPA and DOPAC are seen early and are followed by increased striatal protein carbonyl and 3-nitrotyrosine formation. These changes were associated with decreased striatal dopamine and decreased expression of the dopamine transporter and tyrosine hydroxylase. Furthermore, we observed an increase in α-synuclein immunoreactivity and accumulation and neurodegeneration in the substantia nigra pars compacta in aged VMAT2 LO mice. Thus, VMAT2 LO animals display nigrostriatal degeneration that begins in the terminal fields and progresses to eventual loss of the cell bodies, α-synuclein accumulation, and anl-DOPA responsive behavioral deficit, replicating many of the key aspects of Parkinson's disease. These data suggest that mishandling of dopamine via reduced VMAT2 expression is, in and of itself, sufficient to cause dopamine-mediated toxicity and neurodegeneration in the nigrostriatal dopamine system. In addition, the altered dopamine homeostasis resulting from reduced VMAT2 function may be conducive to pathogenic mechanisms induced by genetic or environmental factors thought to be involved in Parkinson's disease.
GABA Affinity Shapes IPSCs in Thalamic Nuclei
Authors: Schofield Claude M. , Huguenard John R.
Published: July 2007

Precise neural inhibition in thalamocortical circuits is required for the generation of sleep spindles and suppression of hypersynchrony associated with epileptiform activity. Accordingly, the time course of GABAAreceptor-mediated IPSC events is an important parameter influencing the strength of inhibitory signaling. In the thalamus, two distinct types of IPSC kinetics are observed: thalamocortical relay neurons in the ventrobasal nucleus (VB) exhibit a fast decaying IPSC, whereas neurons in the adjacent reticular nucleus (RTN) display a long-lasting, slowly decaying IPSC. Here, we used patch-clamp electrophysiology and computational modeling to elucidate the basis for IPSC kinetic heterogeneity in the thalamus. Rapid application of GABA to excised membrane patches revealed that decay kinetics were attributable to intrinsic differences in GABAAreceptor deactivation. Examination of desensitization and gating properties revealed these to be similar in VB and RTN, with the notable lack of fast and long-lasting desensitized states in both cell types. Computational simulations demonstrate that slow GABA binding and unbinding rates could reproduce the characteristic long-lasting IPSCs in RTN cells. These results indicate that within thalamic circuits, a powerful diversity of inhibitory function can result from simple differences in underlying GABAAreceptor affinity.
Protracted Synaptogenesis after Activity-Dependent Spinogenesis in Hippocampal Neurons
Authors: Nägerl U. Valentin , Köstinger German , Anderson John C. , Martin Kevan A. C. , Bonhoeffer Tobias
Published: July 2007

Activity-dependent morphological plasticity of neurons is central to understanding how the synaptic network of the CNS becomes reconfigured in response to experience. In recent years, several studies have shown that synaptic activation that leads to the induction of long-term potentiation also drives the growth of new dendritic spines, raising the possibility that new synapses are made. We examine this directly by correlating time-lapse two-photon microscopy of newly formed spines on CA1 pyramidal neurons in organotypic hippocampal slices with electron microscopy. Our results show that, whereas spines that are only a few hours old rarely form synapses, older spines, ranging from 15 to 19 h, consistently have ultrastructural hallmarks typical of synapses. This is in agreement with a recentin vivostudy that showed that, after a few days, new spines consistently form functional synapses. In addition, our study provides a much more detailed understanding of the first few hours after activity-dependent spinogenesis. Within tens of minutes, physical contacts are formed with existing presynaptic boutons, which slowly, over the course of many hours, mature into new synapses.
Transcranial Magnetic Stimulation Reveals Two Cortical Pathways for Visual Body Processing
Authors: Urgesi Cosimo , Calvo-Merino Beatriz , Haggard Patrick , Aglioti Salvatore M.
Published: July 2007

Visual recognition of human bodies is more difficult for upside down than upright presentations. This body inversion effect implies that body perception relies on configural rather than local processing. Although neuroimaging studies indicate that the visual processing of human bodies engages a large fronto-temporo-parietal network, information about the neural underpinnings of configural body processing is meager. Here, we used repetitive transcranial magnetic stimulation (rTMS) to study the causal role of premotor, visual, and parietal areas in configural processing of human bodies. Eighteen participants performed a delayed matching-to-sample task with upright or inverted static body postures. Event-related, dual-pulse rTMS was applied 150 ms after the sample stimulus onset, over left ventral premotor cortex (vPMc), right extrastriate body area (EBA), and right superior parietal lobe (SPL) and, as a control site, over the right primary visual cortex (V1). Interfering stimulation of vPMc significantly reduced accuracy of matching judgments for upright bodies. In contrast, EBA rTMS significantly reduced accuracy for inverted but not for upright bodies. Furthermore, a significant body inversion effect was observed after interfering stimulation of EBA and V1 but not of vPMc and SPL. These results demonstrate an active contribution of the fronto-parietal mirror network to configural processing of bodies and suggest a novel, embodied aspect of visual perception. In contrast, the local processing of the body, possibly based on the form of individual body parts instead of on the whole body unit, appears to depend on EBA. Therefore, we propose two distinct cortical routes for the visual processing of human bodies.
Mineralocorticoid Receptor Overexpression Differentially Modulates Specific Phases of Spatial and Nonspatial Memory
Authors: Ferguson Deveroux , Sapolsky Robert
Published: July 2007

Glucocorticoids (GCs) and stress modulate specific phases of information processing. The modulatory affects of GCs on hippocampal function are thought to be mediated by the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). The GR plays a critical role in mediating the impairing effects of GCs on hippocampal function. Conversely, activation of MR facilitates hippocampal function. The high affinity of MR for GCs suggests that the receptor protein levels play a key role in regulating the beneficial effects of MR-mediated gene transcription. Using herpes simplex vectors, we transiently increased MR levels in dentate gyrus granule cells, which in turn enhanced MR signaling. We then examined its effects on spatial and nonspatial memory consolidation and retrieval using the object placement and object recognition task. Additionally, we assessed whether an increased MR signal could block the impairing effects of high GCs on memory retrieval. Rats overexpressing MR displayed an enhancement in the consolidation of nonspatial memory relative to rats expressing green fluorescent protein and suggest the potential for gene transfer techniques for enhancing cognition during stress. Moreover, rats overexpressing MR were spared from the disruptive effects of high GCs on the retrieval of nonspatial memory. Thus, this study illustrates the critical role of MR in mediating the retrieval and consolidation of nonspatial memory.
Neural Mechanisms of Resistance to Peer Influence in Early Adolescence
Authors: Grosbras Marie-Helène , Jansen Marije , Leonard Gabriel , McIntosh Anthony , Osswald Katja , Poulsen Catherine , Steinberg Laurence , Toro Roberto , Paus Tomaš
Published: July 2007

During the shift from a parent-dependent child to a fully autonomous adult, peers take on a significant role in shaping the adolescent's behavior. Peer-derived influences are not always positive, however. Here, we explore neural correlates of interindividual differences in the probability of resisting peer influence in early adolescence. Using functional magnetic resonance imaging, we found striking differences between 10-year-old children with high and low resistance to peer influence in their brain activity during observation of angry hand movements and angry facial expressions: compared with subjects with low resistance to peer influence, individuals with high resistance showed a highly coordinated brain activity in neural systems underlying perception of action and decision making. These findings suggest that the probability of resisting peer influence depends on neural interactions during observation of emotion-laden actions.