bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular and functional identification of organic anion transporter isoforms in cultured bovine mammary epithelial cells (BME‐UV)
Authors: AL‐BATAINEH M. M. , Van Der MERWE D. , SCHULTZ B. D. , GEHRING R.
Published: May 2011

Al‐Bataineh, M. M., van der Merwe, D., Schultz, B. D., Gehring, R. Molecular and functional identification of organic anion transporter isoforms in cultured bovine mammary epithelial cells (BME‐UV). J. vet. Pharmacol. Therap. 35, 209–215.

Mammary epithelial cells express a diversity of membrane transporters including members of organic cation and organic anion (OAT) transporter subfamilies. Four mammal OAT isoforms have been identified: OAT‐1, OAT‐2, OAT‐3, and OAT‐4. The pharmacological significance of OAT isoforms has been emphasized because of their role in the movement of a wide variety of substrates across epithelial barriers. The present study identified (molecularly and functionally) bovine OAT isoforms in bovine mammary epithelial (BME‐UV) cells. mRNA expression levels of all tested transporters in BME‐UV cells were less than expression levels of the corresponding transporters in bovine kidney. Directionality in the flux of P‐aminohippuric acid and acetylsalicylate, compounds known to interact with OAT‐1 and OAT‐2, respectively, across BME‐UV monolayers was not observed at the concentrations used in this study. Directionality was, however, observed in the flux of estrone sulfate (EsS). Adding probenecid, penicillin G or nonradiolabeled EsS to the apical donor compartment significantly increased the apical‐to‐basolateral flux of EsS across the BME‐UV monolayer. These results suggest that BME‐UV cells express an organic anion transport system, making it a potentially useful model to study the role of this transport system in the mammary epithelial barrier.
Onshore record of the subduction of a crustal salient: example of the NW Borneo Wedge
Authors: Sapin François , Pubellier Manuel , Lahfid Abdeltif , Janots Dominik , Aubourg Charles , Ringenbach Jean‐Claude
Published: May 2011

Terra Nova, 23, 232–240, 2011

Subduction of oceanic highs has been described in offshore accretionary wedges thanks to bathymetric and seismic data, and simulated in sand‐box models. Where documented, it is limited to oceanic subduction of small culminations (seamounts). However, tracing this phenomenon in ancient and/or uplifted belts remains a challenge. Based on structural, geomorphological and thermal analysis, we describe a subducted horst in the NW Borneo Wedge. This is evidenced by the occurrence of several geomorphological anomalies: a strong bend of the structural trend of the Rajang–Crocker Belt and an area with ′hummocky′ texture representing dismantled packages of sediments. Some specific structural features (large back and out‐of‐sequence thrusts in the internal zones, complex folds rooted on shear structures in the accretionary wedge) also occur in this central part of the NW Borneo Wedge. The central area of the related deformation zone records several thermal anomalies.

Terra Nova, 00, 1–9, 2011
Are the oroclines of the Variscan belt related to late Variscan strike‐slip tectonics?
Authors: Martínez Catalán José R.
Published: May 2011

Terra Nova, 23, 241–247, 2011

Early Variscan structures and magnetic anomalies delineate four oroclines along the Variscan belt. The arcs bend the lithostratigraphic zones of the autochthon and the allochthonous terranes, which include ophiolites of the Rheic suture and units of Gondwanan derivation subducted on both sides of the Rheic Ocean. A transcurrent model dominated by right‐lateral motion explains the genesis and evolution of the oroclines and a simple plate‐tectonics scenario links late Variscan dextral strike‐slip movements in the Variscides to a broad intracontinental shear zone, kinematically equivalent to a transform fault.

Terra Nova, 00, 1–7, 2011
The key enzyme of sulfate assimilation, adenosine 5′‐phosphosulfate reductase, is regulated by HY5 in Arabidopsis
Authors: Lee Bok‐Rye , Koprivova Anna , Kopriva Stanislav
Published: May 2011

Plant sulfate assimilation is regulated by demand for reduced sulfur, as is its key enzyme, adenosine 5′‐phosphosulfate reductase (APR). In a genetic screen for mutants lacking this regulation, we identified the bZIP transcription factor LONG HYPOCOTYL 5 (HY5) as a necessary component of the regulatory circuit. Regulation of APR activity by the inhibitor of glutathione synthesis, buthionine sulfoximine, or by the precursor of cysteine, O‐acetylserine, was disrupted in the hy5 mutant. When dark‐adapted plants were re‐illuminated, the rapid induction of APR1 and APR2 mRNA levels was attenuated in hy5 seedlings, but APR3 regulation was not affected. Chromatin immunoprecipitation revealed that HY5 binds directly to the APR1 and APR2 promoters but not to the APR3 promoter. Accordingly, the regulation of APR1 and APR2 by O‐acetylserine was disturbed in hy5 roots. HY5 is also important for the coordination of nitrogen and sulfur assimilation, as, unlike the wild‐type, hy5 mutants do not undergo a reduction in sulfate uptake and APR activity during nitrogen starvation. Altogether, these data show that HY5 plays an important role in regulation of APR gene expression and plant sulfate assimilation.
Dual functions of the nucleus‐encoded factor TDA1 in trapping and translation activation of atpA transcripts in Chlamydomonas reinhardtii chloroplasts
Authors: Eberhard Stephan , Loiselay Christelle , Drapier Dominique , Bujaldon Sandrine , Girard‐Bascou Jacqueline , Kuras Richard , Choquet Yves , Wollman Francis‐André
Published: May 2011

After endosymbiosis, organelles lost most of their initial genome. Moreover, expression of the few remaining genes became tightly controlled by the nucleus through trans‐acting protein factors that are required for post‐transcriptional expression (maturation/stability or translation) of a single (or a few) specific organelle target mRNA(s). Here, we characterize the nucleus‐encoded TDA1 factor, which is specifically required for translation of the chloroplast atpA transcript that encodes subunit α of ATP synthase in Chlamydomonas reinhardtii. The sequence of TDA1 contains eight copies of a degenerate 38‐residue motif, that we named octotrico peptide repeat (OPR), which has been previously described in a few other trans‐acting factors targeted to the C. reinhardtii chloroplast. Interestingly, a proportion of the untranslated atpA transcripts are sequestered into high‐density, non‐polysomic, ribonucleoprotein complexes. Our results suggest that TDA1 has a dual function: (i) trapping a subset of untranslated atpA transcripts into non‐polysomic complexes, and (ii) translational activation of these transcripts. We discuss these results in light of our previous observation that only a proportion of atpA transcripts are translated at any given time in the chloroplast of C. reinhardtii.
BON1 interacts with the protein kinases BIR1 and BAK1 in modulation of temperature‐dependent plant growth and cell death in Arabidopsis
Authors: Wang Zheng , Meng Pei , Zhang Xiaoyan , Ren Dongtao , Yang Shuhua
Published: May 2011

The Arabidopsis copine gene BON1 encodes a calcium‐dependent phospholipid‐binding protein involved in plant growth homeostasis and disease resistance. However, the biochemical and molecular mechanisms by which BON1 modulates plant growth and defense responses are not well understood. Here, we show that BON1 interacts physically with the leucine‐rich‐repeat receptor‐like kinases BIR1 (BAK1‐interacting receptor‐like kinase 1) and pathogen‐associated molecular pattern (PAMP) receptor regulator BAK1 in vitro and in vivo. Additionally, bon1 and bir1 mutants exhibit synergistic interaction. While a bir1 null mutant has similar growth and cell‐death defects compared with bon1, a bir1 bon1 double mutant displays more severe phenotypes than does the single mutants. The bon1‐1 and bir1‐1 phenotypes are partially suppressed by overexpression of BIR1 and BON1, respectively. Furthermore, the bir1 phenotype is attenuated by a loss‐of‐function mutation in the resistance (R) gene SNC1 (Suppressor of npr1‐1, constitutive 1), which mediates defense responses in bon1. Intriguingly, BON1 and BIR1 can be phosphorylated by BAK1 in vitro. Our findings suggest that BIR1 functions as a negative regulator of plant resistance and that BON1 and BIR1 might modulate both PAMP‐ and R protein‐triggered immune responses.
Integrating long‐day flowering signals: a LEAFY binding site is essential for proper photoperiodic activation of APETALA1
Authors: Benlloch Reyes , Kim Min Chul , Sayou Camille , Thévenon Emmanuel , Parcy Francois , Nilsson Ove
Published: May 2011

The transition to flowering in Arabidopsis is characterized by the sharp and localized upregulation of APETALA1 (AP1) transcription in the newly formed floral primordia. Both the flower meristem‐identity gene LEAFY (LFY) and the photoperiod pathway involving the FLOWERING LOCUS T (FT) and FD genes contribute to this upregulation. These pathways have been proposed to act independently but their respective contributions and mode of interaction have remained elusive. To address these questions, we studied the AP1 regulatory region. Combining in vitro and in vivo approaches, we identified which of the three putative LFY binding sites present in the AP1 promoter is essential for its activation by LFY. Interestingly, we found that this site is also important for the correct photoperiodic‐dependent upregulation of AP1. In contrast, a previously proposed putative FD‐binding site appears dispensable and unable to bind FD and we found no evidence for FD binding to other sites in the AP1 promoter, suggesting that the FT/FD‐dependent activation of AP1 might be indirect. Altogether, our data give new insight into the interaction between the FT and LFY pathways in the upregulation of AP1 transcription under long‐day conditions.
Revealing impaired pathways in the an11 mutant by high‐throughput characterization of Petunia axillaris and Petunia inflata transcriptomes
Authors: Zenoni Sara , D’Agostino Nunzio , Tornielli Giovanni B. , Quattrocchio Francesca , Chiusano Maria L. , Koes Ronald , Zethof Jan , Guzzo Flavia , Delledonne Massimo , Frusciante Luigi , Gerats Tom , Pezzotti Mario
Published: May 2011

Petunia is an excellent model system, especially for genetic, physiological and molecular studies. Thus far, however, genome‐wide expression analysis has been applied rarely because of the lack of sequence information. We applied next‐generation sequencing to generate, through de novo read assembly, a large catalogue of transcripts for Petunia axillaris and Petunia inflata. On the basis of both transcriptomes, comprehensive microarray chips for gene expression analysis were established and used for the analysis of global‐ and organ‐specific gene expression in Petunia axillaris and Petunia inflata and to explore the molecular basis of the seed coat defects in a Petunia hybrida mutant, anthocyanin 11 (an11), lacking a WD40‐repeat (WDR) transcription regulator. Among the transcripts differentially expressed in an11 seeds compared with wild type, many expected targets of AN11 were found but also several interesting new candidates that might play a role in morphogenesis of the seed coat. Our results validate the combination of next‐generation sequencing with microarray analyses strategies to identify the transcriptome of two petunia species without previous knowledge of their genome, and to develop comprehensive chips as useful tools for the analysis of gene expression in P. axillaris, P. inflata and P. hybrida.
Multicentre prospective study on dengue classification in four South‐east Asian and three Latin American countries
Authors: Alexander Neal , Balmaseda Angel , Coelho Ivo C. B. , Dimaano Efren , Hien Tran T. , Hung Nguyen T. , Jänisch Thomas , Kroeger Axel , Lum Lucy C. S. , Martinez Eric , Siqueira Joao B. , Thuy Tran T. , Villalobos Iris , Villegas Elci , Wills Bridget ,   on behalf of the European Union, World Health Organization (WHO‐TDR) supported DENCO Study Group
Published: May 2011

Objective  To evaluate the existing WHO dengue classification across all age groups and a wide geographical range and to develop a revised evidence‐based classification that would better reflect clinical severity.

Methods  We followed suspected dengue cases daily in seven countries across South‐east Asia and Latin America and then categorised them into one of three intervention groups describing disease severity according to the overall level of medical and nursing support required. Using a pre‐defined analysis plan, we explored the clinical and laboratory profiles characteristic of these intervention categories and presented the most promising options for a revised classification scheme to an independent group of WHO dengue experts for consideration. Potential warning signs were also evaluated by comparing contemporaneous data of patients who progressed to severe disease with the data of those who did not.

Results  A total of 2259 patients were recruited during 2006–2007 and 230 (13%) of the 1734 laboratory‐confirmed patients required major intervention. Applying the existing WHO system, 47/210 (22%) of patients with shock did not fulfil all the criteria for dengue haemorrhagic fever. However, no three‐tier revision adequately described the different severity groups either. Inclusion of readily discernible complications (shock/severe vascular leakage and/or severe bleeding and/or severe organ dysfunction) was necessary to devise a system that identified patients requiring major intervention with sufficient sensitivity and specificity to be practically useful. Only a small number of subjects (5%) progressed to severe disease while under observation; several warning signs were identified, but much larger studies are necessary to fully characterize features associated with disease progression.

Conclusions  Based on these results, a revised classification system comprised of two entities, ‘Dengue’ and ‘Severe Dengue’, was proposed and has now been incorporated into the new WHO guidelines.
Monitoring drug effectiveness in kala‐azar in Bihar, India: cost and feasibility of periodic random surveys vs. a health service‐based reporting system
Authors: Malaviya P. , Singh R. P. , Singh S. P. , Hasker E. , Ostyn B. , Shankar R. , Boelaert M. , Sundar S.
Published: May 2011

Objective  In 2009, a random survey was conducted in Muzaffarpur district to document the clinical outcomes of visceral leishmaniasis patients (VL) treated by the public health care system in 2008, to assess the effectiveness of miltefosine against VL. We analysed the operational feasibility and cost of such periodic random surveys as compared with health facility‐based routine monitoring.

Methods  A random sample of 150 patients was drawn from registers kept at Primary Health Care centres. Patient records were examined, and the patients were located at their residence. Patients and physicians were interviewed with the help of two specifically designed questionnaires by a team of one supervisor, one physician and one field worker. Costs incurred during this survey were properly documented, and vehicle log books maintained for analysis.

Results  Hundred and 39 (76.7%) of the patients could be located. Eleven patients were not traceable. Per patient, follow‐up cost was US$ 15.51 and on average 2.27 patients could be visited per team‐day. Human resource involvement constituted 75% of the total cost whereas involvement of physician costs 51% of the total cost.

Conclusion  A random survey to document clinical outcomes is costly and labour intensive but gives probably the most accurate information on drug effectiveness. A health service‐based retrospective cohort reporting system modelled on the monitoring system developed by tuberculosis programmes could be a better alternative. Involvement of community health workers in such monitoring would offer the additional advantage of treatment supervision and support.
The effect of oral isotretinoin (13‐cis retinoic acid) on hearing systems in patients with acne vulgaris: a prospective study
Authors: Karabulut Hayriye , Karadag Ayse Serap , Acar Baran , Dagli Muharrem , Karabulut Ismail , Ozmen Erkan , Babademez Mehmet Ali , Karaşen Rıza Murat
Published: May 2011

Isotretinoin is widely used in the treatment of extensive and nodulocystic acne. The objective of this prospective study was to investigate whether oral isotretinoin could affect the hearing system. Thirty‐eight patients with acne vulgaris (76 ears) who were diagnosed and treated at the Department of Dermatology were included in the current study. Study evaluation visits were performed at baseline and at Weeks 1, 2 and 3. Pure‐tone averages (PTAs) of air conduction thresholds at 250 Hz (PTA1); 500, 1000, and 2000 Hz (PTA2); 4000, 8000, and 10, 000 Hz (PTA3); and 12, 500, 16, 000, 18, 000 and 20, 000 Hz (PTA4) for each ear were calculated separately. Assessment of the efficacy was based on the audiometric findings. Compared with pre‐treatment evaluation, the PTAs of patients were found to be significantly different at the first week for PTA2 (P = 0.033) and PTA3 (P = 0.001), at the second week for PTA1 (P = 0.036), and at the third week for PTA4 (P = 0.002). Our results suggest that the oral isotretinoin (13‐cis retinoic acid), which is a derivative of retinol (vitamin A), improved the hearing level of the patients in all audiometric frequencies in a short‐period follow‐up.
Imagined futures: how experiential knowledge of disability affects parents’ decision making about fetal abnormality
Authors: France Emma F. , Locock Louise , Hunt Kate , Ziebland Sue , Field Kate , Wyke Sally
Published: May 2011

Background  Knowledge of disability is considered key information to enable informed antenatal screening decisions by expectant parents. However, little is known about the role of experiential knowledge of disability in decisions to terminate or continue with a pregnancy diagnosed with a fetal abnormality.

Objective  To explore the role that expectant parents’ experiential knowledge of disabilities and conditions can play in real‐life decisions to continue or end a pregnancy with a fetal abnormality.

Design  Secondary analysis of qualitative narrative interview data informed by contextual systems framework.

Setting  Participants were recruited throughout the United Kingdom and interviewed between 2004 and 2006.

Participants  Twenty‐four women and four of their male partners who had direct or indirect experience of disability or illness and who had proceeded with or ended a pregnancy diagnosed with a fetal abnormality.

Findings  Most respondents recounted using their experiential knowledge of disability, whether of their unborn baby’s condition or of a different condition, to try to imagine the future for their unborn child, themselves and their family when making their decision. Some, who were considering continuing their pregnancy and had little or no experience of their unborn baby’s specific disability, sought out others’ experiences of the condition following antenatal diagnosis.The nature of a parent’s experiential knowledge did not predict whether they continued with or terminated their pregnancy.

Discussion  Prospective parents may find it helpful to discuss their existing knowledge of their unborn baby’s condition with health professionals who are aware of the influence this might have on parents’ decisions.
Fathers’ contributions to the management of their child’s long‐term medical condition: a narrative review of the literature
Authors: Swallow Veronica , Macfadyen Ann , Santacroce Sheila J. , Lambert Heather
Published: May 2011

Context  Fathers’ contributions to the management of long‐term childhood medical conditions are under‐represented in the literature; therefore, the full extent of their involvement is poorly understood by practitioners and researchers, so strategies for promoting their involvement have not yet been fully considered.

Objective  To review studies of fathers’ actual contributions in a wide range of conditions, the potential to optimize their contribution through additional interventions by health professionals and a direction for future research.

Design  Narrative review of the literature.

Methods  CINAHL, Medline, PsychInfo and ERIC databases were searched electronically between the years 1995–2008. The terms adherence, adjustment, child, chronic, compliance, concordance, condition, coping, disease, father, illness, information, long‐term, management/intervention, mother, role, self‐care and treatment were searched for separately and in combination. English language papers reporting primary research were selected and supplemented by hand‐searching reference lists. Thirty‐five papers (arising from 29 studies) met criteria and were selected for narrative review.

Results  Five themes were identified: (i) the impact of long‐term conditions on fathers’ ability to promote their child’s well‐being, (ii) factors influencing fathers’ involvement in health care, (iii) personal growth/beneficial effects for fathers, (iv) the impact of father’s involvement on family functioning and (v) strategies that increase fathers’ participation in their child’s health care and in research investigating fathers’ participation.

Conclusions  The review suggests that fathers’ involvement in children’s health care can positively impact on fathers’, mothers’ and children’s well‐being and family functioning. A range of strategies are identified to inform the promotion of fathers’ contributions and future research investigating their input.
How should patients behave to facilitate shared decision making – the doctors’ view
Authors: Hamann Johannes , Mendel Rosmarie , Bühner Markus , Kissling Werner , Cohen Rudolf , Knipfer Eva , Eckstein Hans‐Henning
Published: May 2011

Objective  To study how physicians feel about patients’ efforts to be engaged in shared decision making (SDM).

Study setting and design  Survey of physicians from distinctly different medical disciplines (238 psychiatrists and 169 vascular surgeons). Participants were requested to judge which patient behaviours they find helpful and which behaviours detrimental for SDM.

Results  Psychiatrists and surgeons had rather positive attitudes about active patient behaviours. However, there were quite a few patient behaviours (e.g. searching the Internet, being assertive towards the doctor) which provoked ambivalent or negative attitudes.

Discussion and conclusions  Physicians are generally quite open towards active patient behaviour in the consultation. They, however, do consider it as less helpful and become more annoyed if patients insist on their preferences and doubt their doctors’ recommendations. Physicians must realize that SDM implies giving up decisional power and try to be more flexible in their interactions with patients.
Defining and measuring patient‐centred care: an example from a mixed‐methods systematic review of the stroke literature
Authors: Lawrence Maggie , Kinn Sue
Published: May 2011

Background  Involving patients in the determination of their care is increasingly important, and health‐care professionals worldwide have recognized a need for clinical outcome measures and interventions that facilitate patient‐centred care delivery in a range of settings.

Aim  A mixed‐methods review was conducted, which aimed to identify stroke‐specific patient‐centred outcome measures and patient‐centred interventions.

Search strategy  Databases searched included MEDLINE and PsycINFO; search strings were based on MeSH terms and keywords associated with the terms ‘stroke’ and ‘patient‐centred’.

Data extraction and analysis  Descriptive statistics were used to report quantitative data; thematic analysis was also performed in the included studies.

Main Results  Three patient‐centred outcome measures (Subjective Index of Physical and Social Outcomes, Stroke Impact Scale, Communication Outcome after Stroke scale) and four interventions were identified. Key elements of intervention design included delivery in people’s own homes, involvement of families and tailoring to individual needs and priorities. Thematic analysis enabled description of three broad themes: meaningfulness and relevance, quality, and communication, which informed the development of a definition of patient‐centred care specific to the specialty of stroke.

Conclusions  It is important for health‐care professionals to ensure that their practice is relevant to patients and families. The review identified three stroke‐specific patient‐centred outcome measures, key elements of patient‐centred interventions, and informed the development of a definition of patient‐centred care. These review‐derived outputs represent a useful starting point for health‐care professionals, whatever their specialty, who are working to reconcile tensions between priorities of health‐care professionals and those of patients and their families, to ensure delivery of patient‐centred care.
Putting the ‘patient’ in patient safety: a qualitative study of consumer experiences
Authors: Rathert Cheryl , Brandt Julie , Williams Eric S.
Published: May 2011

Background  Although patient safety has been studied extensively, little research has directly examined patient and family (consumer) perceptions. Evidence suggests that clinicians define safety differently from consumers, e.g. clinicians focus more on outcomes, whereas consumers may focus more on processes. Consumer perceptions of patient safety are important for several reasons. First, health‐care policy leaders have been encouraging patients and families to take a proactive role in ensuring patient safety; therefore, an understanding of how patients define safety is needed. Second, consumer perceptions of safety could influence outcomes such as trust and satisfaction or compliance with treatment protocols. Finally, consumer perspectives could be an additional lens for viewing complex systems and processes for quality improvement efforts.

Objectives  To qualitatively explore acute care consumer perceptions of patient safety.

Design and methods  Thirty‐nine individuals with a recent overnight hospital visit participated in one of four group interviews. Analysis followed an interpretive analytical approach.

Results  Three basic themes were identified: Communication, staffing issues and medication administration. Consumers associated care process problems, such as delays or lack of information, with safety rather than as service quality problems. Participants agreed that patients need family caregivers as advocates.

Conclusions  Consumers seem acutely aware of care processes they believe pose risks to safety. Perceptual measures of patient safety and quality may help to identify areas where there are higher risks of preventable adverse events.
(Un)organizing equal collaboration between users and professionals: on management of patient education in Norway
Authors: Stokken Roar
Published: May 2011

Background  This is an article about how patient education is managed in Norway, but it also addresses a matter of broader relevance that of how an organization imbued with a request for rational choices is able to take on board a contradictory ideology. In Norway, patient education under the auspice of hospitals is to be conducted as an equal collaboration between users and professionals, posing challenges to the ethos of rationally justified choices within the hospital sector. This calls for an exploration of how the organization copes with the contradictory demands.

Methods  A theoretical approach on the basis of theories from Scandinavian institutional theory and science and technology studies, informed by documents, interviews and experiences from national, regional and local levels in Norway.

Discussion  The field of patient education is divided into three decoupled domains: one at management level, one at the practical level, and in the middle a domain that acts as an interface between management and practice. This interface mediates the relationship between ideas and practice, without making overt the fact that ideas might not be possible to put into practice and that practice might not reflect ideas.

Conclusions  The decoupling of practice and management allows patient education as equal collaboration between users and professionals to thrive as an idea, not subjugated by practical challenges. Thus, it can exist as a guiding star that both management and practitioners can attune to, but this situation might now be threatened by the demand for quality assurance in the field.
Evidence for disease penetrance relating to CNV size: Pelizaeus–Merzbacher disease and manifesting carriers with a familial 11 Mb duplication at Xq22
Authors: Carvalho CMB , Bartnik M , Pehlivan D , Fang P , Shen J , Lupski JR
Published: May 2011

Carvalho CMB, Bartnik M, Pehlivan D, Fang P, Shen J, Lupski JR. Evidence for disease penetrance relating to CNV size: Pelizaeus–Merzbacher disease and manifesting carriers with a familial 11 Mb duplication at Xq22.

The potential causes for the incomplete penetrance of Pelizaeus–Merzbacher disease (PMD) in female carriers of PLP1 mutations are not well understood. We present a family with a boy having PMD in association with PLP1 duplication and three females who are apparent manifesting carriers. Custom high‐resolution oligonucleotide array comparative genomic hybridization (aCGH) and breakpoint junction sequencing were performed and revealed a familial complex duplication consisting of a small duplicated genomic interval (∼56 kb) and a large segmental duplication (∼11 Mb) that resulted in a PLP1 copy number variation gain. Breakpoint junction analysis implicates a replication‐based mechanism underlying the rearrangement formation. X‐inactivation studies (XCI) showed a random to moderate advantageous skewing pattern in peripheral blood cells but a moderate to extremely skewed (≥90%) pattern in buccal cells. In conclusion, our data show that complex duplications involving PLP1 are not uncommon, can be detected at the level of genome resolution afforded by clinical aCGH and duplication and inversion can be produced in the same event. Furthermore, the observation of three manifesting carriers with a large genomic rearrangement supports the contention that duplication size along with genomic content can be an important factor for penetrance of the PMD phenotype in females.
Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2
Authors: Crimella C , Baschirotto C , Arnoldi A , Tonelli A , Tenderini E , Airoldi G , Martinuzzi A , Trabacca A , Losito L , Scarlato M , Benedetti S , Scarpini E , Spinicci G , Bresolin N , Bassi MT
Published: May 2011

Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT. Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2.

Spastic paraplegia type 10 (SPG10) is an autosomal dominant form of hereditary spastic paraplegia (HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy chain implicated in anterograde axonal transport. KIF5A mutations were found in both pure and complicated forms of the disease; a single KIF5A mutation was also detected in a CMT2 patient belonging to an SPG10 mutant family. To confirm the involvement of the KIF5A gene in both CMT2 and SPG10 phenotypes and to define the frequency of KIF5A mutations in an Italian HSP patient population, we performed a genetic screening of this gene in a series of 139 HSP and 36 CMT2 affected subjects. We identified five missense changes, four in five HSP patients and one in a CMT2 subject. All mutations, including the one segregating in the CMT2 patient, are localized in the kinesin motor domain except for one, falling within the stalk domain and predicted to generate protein structure destabilization. The results obtained indicate a KIF5A mutation frequency of 8.8% in the Italian HSP population and identify a region of the kinesin protein, the stalk domain, as a novel target for mutation. In addition, the mutation found in the CMT2 patient strengthens the hypothesis that CMT2 and SPG10 are the extreme phenotypes resulting from mutations in the same gene.
Fabry disease ‘The New Great Imposter’: results of the French Observatoire in Internal Medicine Departments (FIMeD)
Authors: Lidove O , Kaminsky P , Hachulla E , Leguy‐Seguin V , Lavigne C , Marie I , Maillot F , Serratrice C , Masseau A , Chérin P , Cabane J , Noel E ,   on behalf of the FIMeD investigators
Published: May 2011

Lidove O, Kaminsky P, Hachulla E, Leguy‐Seguin V, Lavigne C, Marie I, Maillot F, Serratrice C, Masseau A, Chérin P, Cabane J, Noel E; on behalf of the FIMeD investigators. Fabry disease ‘The New Great Imposter’: results of the French Observatoire in Internal Medicine Departments (FIMeD).

Fabry disease (FD) is an X‐linked lysosomal storage disorder due to α‐galactosidase A deficiency. It is associated with a broad range of clinical symptoms, resulting in frequent misdiagnosis and diagnostic delay, which may impact on patient outcomes. This retrospective observational study of 58 FD patients referred to 10 internal medicine departments in France aimed to review differential diagnoses received prior to diagnosis and examines diagnostic delay. The average age at the time of diagnosis was 27.6 years (range: 10–60) and 42.2 years (range: 9–77) among the 23 males and 35 females analyzed, respectively. Most common symptoms that led to FD diagnosis were family history of FD (12 males and 27 females), followed by pain in extremities (10 males and 5 females), and angiokeratoma (8 males and 4 females). Eighteen patients had received alternative diagnoses prior to FD diagnosis, including a female patient with four previous diagnoses. Four case reports are presented, which illustrate the diagnostic ‘odyssey’ and delayed diagnosis often experienced by patients. Clinicians should consider a diagnosis of FD when presented with a wide range of symptoms, thus helping to shorten the diagnostic delay and facilitating early therapy with enzyme replacement therapy to improve patient outcomes.
Identification of the novel HLA‐B allele B*57:29 by cloning and sequencing in a Chinese individual
Authors: Gao S.‐Q. , Xu Y.‐P. , Deng Zh.‐H.
Published: May 2011

HLA‐B plays an important role in unrelated donor hematopoietic stem cell transplantation.
Two novel HLA‐A alleles: HLA‐A*31:01:09 and HLA‐A*33:30
Authors: Ji Y. , Sun Y. , Liu Y. , Xie J. , Du K.
Published: May 2011

The HLA‐A*31:01:09 differs from the closest allele HLA‐A*31:01:02 by a C to T silent substitution at position 447 in exon 3. The HLA‐A*33:30 differs from the closest allele HLA‐A*33:03:01 by a single nucleotide substitution at position 453 in exon 3, leading to a change of Arg131Cys.
Identification of a novel allele HLA‐DRB1*08:41 in a Chinese donor
Authors: Sun L.‐J. , Hu J. , Tan T. , Guo H. , Gao J.‐W.
Published: May 2011

HLA‐DRB1*08:41 shows seven nucleotide differences from DRB1*08:18 and result in three amino acid changes.
Sequencing‐based typing identifies three new HLA alleles: C*02:29, C*06:29 and DQB1*03:24
Authors: Nguyen T. K. T. , Giannoli C. , Favre‐Victoire I. , Dubois V.
Published: May 2011

Two new HLA‐C alleles, C*02:29 and C*06:29, and one new HLA‐DQB1 allele, DQB1*03:24, are described.
Association of IL‐12p40 +1188 A/C polymorphism with nasopharyngeal cancer risk and tumor extension
Authors: Ben Chaaben A. , Busson M. , Douik H. , Boukouaci W. , Mamoghli T. , Chaouch L. , Harzallah L. , Dorra S. , Fortier C. , Ghanem A. , Charron D. , Krishnamoorthy R. , Guemira F. , Tamouza R.
Published: May 2011

The interleukin 12 (IL‐12) cytokine, encoded by polymorphic genes, plays a central role in the T helper 1 cell‐mediated immunity against tumors. We investigated whether the 3′ untranslated region +1188 A/C polymorphism (rs 3212227) influences the nasopharyngeal carcinoma (NPC) risk in Tunisian patients. DNA analysis of 247 patients and 284 healthy individuals showed a higher frequency of the 1188 C allele and the CC genotype in patients than in controls (P = 0.00001and P = 0.00005) suggesting that the C variant allele is associated with the susceptibility to NPC. Additional testing showed that the homozygous CC genotype is also associated with advanced stage of the tumor extension at presentation (P = 0.022). Our data suggest that the impaired production of IL‐12 behaves as a risk factor for NPC occurrence and progression.
Breed‐independent toll‐like receptor 5 polymorphisms show association with canine inflammatory bowel disease
Authors: Kathrani A. , House A. , Catchpole B. , Murphy A. , Werling D. , Allenspach K.
Published: May 2011

Inflammatory bowel disease (IBD) is thought to be the most common cause of vomiting and diarrhoea in dogs. Although IBD can occur in any canine breed, certain breeds are more susceptible. We have previously shown that polymorphisms in theTLR4andTLR5(toll‐like receptor) genes are significantly associated with IBD in German Shepherd dogs (GSDs). In order to allow for the development of novel diagnostics and therapeutics suitable for all dogs suffering from IBD, it would be useful to determine if the described polymorphisms are also significantly associated with IBD in other breeds. Therefore, the aim of this study was to investigate whether polymorphisms in the canineTLR4andTLR5genes are associated with IBD in other non‐GSD canine breeds. The significance of the previously identified non‐synonymous single nucleotide polymorphisms (SNPs) in theTLR4(T23C, G1039A, A1571T and G1807A) andTLR5genes (G22A, C100T and T1844C) were evaluated in a case‐control study using a SNaPSHOT multiplex reaction. Sequencing information from 85 unrelated dogs with IBD consisting of 38 different breeds was compared with a breed‐matched control group consisting of 162 unrelated dogs. Indeed, as in the GSD IBD population, the twoTLR5SNPs (C100T and T1844C) were found to be significantly protective for IBD in other breeds (P= 0.023 andP= 0.0195 respectively). Our study suggests that the twoTLR5SNPs, C100T and T1844C could play a role in canine IBD as these were found to be protective factors for this disease in 38 different canine breeds. Thus, targetingTLR5in the canine system may represent a suitable way to develop new treatment for IBD in dogs.
A new method for typing bovine major histocompatibility complex class II DRB3 alleles by combining two established PCR sequence‐based techniques
Authors: Takeshima S.‐N. , Matsumoto Y. , Miyasaka T. , Arainga‐Ramirez M. , Saito H. , Onuma M. , Aida Y.
Published: May 2011

Recently, two polymerase chain reaction sequence‐based typing (PCR‐SBT) methods were reported for the genotyping of the bovine leukocyte antigen (BoLA)‐DRB3. One technique is a single PCR‐SBT (sPCR‐SBT) method that generates heterozygous sequences that are subsequently analyzed by the haplofinder program, while the other technique is a nested PCR‐SBT (nPCR‐SBT) method that allows the analysis of heterozygous sequences using the assign 400ATF software. In this study, these techniques were compared and then integrated to produce an improved genotyping method. The primer set used for sPCR‐SBT was more accurate than those used for nPCR‐SBT. Combining sPCR‐SBT with the assign 400ATF software previously reported for nPCR‐SBT enables rapid and accurate genotyping of a large number of DNA samples.
Lack of KIR2DL4 gene in a fertile Caucasian woman
Authors: Nowak I. , Majorczyk E. , Płoski R. , Senitzer D. , Sun J. Y. , Kuśnierczyk P.
Published: May 2011

Killer cell immunoglobulin‐like receptor (KIR2DL4) gene is present in virtually all humans. It encodes a receptor present on uterine and decidual natural killer (NK) cells and some peripheral blood NK cells. Its only known ligand is human leukocyte antigen‐G molecule expressed on extravillous trophoblasts invading the decidua. Therefore, KIR2DL4 has been regarded as a molecule important for successful pregnancy. However, a multiparous woman from Africa, lacking KIR2DL4 gene, was described suggesting that this gene is not absolutely required for successful human reproduction. Here, we describe a Polish woman who delivered a child and who is not only lacking KIR2DL4 gene, but also possessing a KIR genotype virtually identical to that of the African woman mentioned above. Their genotypes are compared with few other KIR2DL4‐negative genotypes and haplotypes described so far.
Identification of the new HLA‐A*31:48 allele in an Italian patient
Authors: Testi M. , Battarra M. , Troiano M. , Condello R. , Andreani M.
Published: May 2011

Human leukocyte antigen (HLA) class I sequence‐based typing (SBT) for hematopoietic unrelated donor searching in an Italian Caucasian patient showed the presence of a novel HLA‐A allele defined as A*31:48. HLA‐A*31:48 has one nucleotide change from A*31:01:02 at nt 727 from C to T, resulting in an amino acid change at codon 219 of exon 4 from Arg to Trp.
Stomatal factors and vulnerability of stem xylem to cavitation in poplars
Authors: Arango‐Velez Adriana , Zwiazek Janusz J. , Thomas Barb R. , Tyree Melvin T.
Published: May 2011

The relationships between the vulnerability of stem xylem to cavitation, stomatal conductance, stomatal density, and leaf and stem water potential were examined in six hybrid poplar (P38P38, Walker, Okanese, Northwest, Assiniboine and Berlin) and balsam poplar (Populus balsamifera) clones. Stem xylem cavitation resistance was examined with the Cavitron technique in well‐watered plants grown in the greenhouse. To investigate stomatal responses to drought, plants were subjected to drought stress by withholding watering for 5 (mild drought) and 7 (severe drought) days and to stress recovery by rewatering severely stressed plants for 30 min and 2 days. The clones varied in stomatal sensitivity to drought and vulnerability to stem xylem cavitation. P38P38 reduced stomatal conductance in response to mild stress while the balsam poplar clone maintained high leaf stomatal conductance under more severe drought stress conditions. Differences between the severely stressed clones were also observed in leaf water potentials with no or relatively small decreases in Assiniboine, P38P38, Okanese and Walker. Vulnerability to drought‐induced stem xylem embolism revealed that balsam poplar and Northwest clones reached loss of conductivity at lower stem water potentials compared with the remaining clones. There was a strong link between stem xylem resistance to cavitation and stomatal responsiveness to drought stress in balsam poplar and P38P38. However, the differences in stomatal responsiveness to mild drought suggest that other drought‐resistant strategies may also play a key role in some clones of poplars exposed to drought stress.
Comparative therapeutic efficacy and safety of type‐II collagen (uc‐II), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate
Authors: Gupta R. C. , Canerdy T. D. , Lindley J. , Konemann M. , Minniear J. , Carroll B. A. , Hendrick C. , Goad J. T. , Rohde K. , Doss R. , Bagchi M. , Bagchi D.
Published: May 2011

The investigation was conducted on client‐owned moderately arthritic dogs with two objectives: (i) to evaluate therapeutic efficacy of type‐II collagen (UC‐II) alone or in combination with glucosamine hydrochloride (GLU) and chondroitin sulphate (CHO), and (ii) to determine their tolerability and safety. Dogs in four groups (n = 7–10), were treated daily for a period of 150 days with placebo (Group‐I), 10 mg active UC‐II (Group‐II), 2000 mg GLU + 1600 mg CHO (Group‐III), and UC‐II + GLU + CHO (Group‐IV). On a monthly basis, dogs were evaluated for observational pain (overall pain, pain upon limb manipulation, and pain after physical exertion) using different numeric scales. Pain level was also measured objectively using piezoelectric sensor‐based GFP for peak vertical force and impulse area. Dogs were also examined every month for physical, hepatic (ALP, ALT and bilirubin) and renal (BUN and creatinine) functions. Based on observations, significant (p < 0.05) reduction in pain was noted in Group‐II, III, and IV dogs. Using GFP, significant increases in peak vertical force (N/kg body wt) and impulse area (N s/kg body wt), indicative of a decrease in arthritis associated pain, were observed in Group‐II dogs only. None of the dogs in any group showed changes in physical, hepatic or renal functions. In conclusion, based on GFP data, moderately arthritic dogs treated with UC‐II (10 mg) showed a marked reduction in arthritic pain with maximum improvement by day 150. UC‐II, GLU and CHO operate through different mechanisms of action, and were well tolerated over a period of 150 days.
Modulation of electrogenic transport processes in the porcine proximal colon by enteric neurotransmitters
Authors: Pfannkuche H. , Mauksch A. , Gäbel G.
Published: May 2011

The aim of our study was to evaluate the involvement of essential pro‐ and antisecretory neurotransmitters in regulation of secretion in porcine proximal colon. Choline acetyltransferase (ChAT), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), substance P (SP), somatostatin (SOM) and neuropeptide Y (NPY) were located immunohistochemically in the epithelium and subepithelial layer. Modulation of epithelial secretion was studied in Ussing chambers. Application of carbachol (CA), sodium nitroprussid (SNP), VIP and SP but not of NPY or SOM resulted in a chloride dependent increase in short circuit current (Isc). Isc increase induced by CA, VIP or SNP was not altered by preincubation with tetrodotoxin or indomethacin. In contrast, SP‐induced Isc increase was diminished by preincubation with tetrodotoxin, indomethacin, l‐nitro‐arginin‐methyl‐ester, and atropine but not hexamethonium. Simultaneous application of CA and VIP, or CA and SNP increased the Isc stronger as expected. Applying SP/CA led to a smaller increase in Isc as calculated. It is concluded that mainly prosecretory neurotransmitters are involved in regulation of colonic secretion. Cross‐potentiations of acetylcholine and nitric oxide and acetylcholine and VIP suggest activation of different intracellular cascades. Similar intracellular pathways may be stimulated by acetylcholine and SP, thus preventing an additive effect of the transmitters.
Correlation between phospholipase of Candida albicans and resistance to fluconazole
Authors: Ying Su , Chunyang Li
Published: May 2011

The objective of this study was to compare phospholipase production between fluconazole‐resistant and fluconazole‐susceptible strains of Candida albicans in order to explore the relationship between resistance to antifungal drugs and virulence of C. albicans. Fifteen each of fluconazole‐resistant (MIC ≥ 64 μg ml−1) and fluconazole‐susceptible (MIC ≤ 8 μg ml−1) strains of C. albicans were incubated on egg yolk agar to detect phospholipase activity. Virulence of C. albicans was assessed by the average survival time of infected mice. Expression of phospholipase B1 mRNA and protein were detected by RT‐PCR and Western blot method. Significant differences between the two groups of Candida strains were observed in phospholipase activity and average survival time of infected mice. The expression of phospholipase B1 mRNA and protein (both of secreted and intracellular forms) were higher in resistant strains than in susceptible strains. The results indicate that the phospholipase activity of C. albicans may be related to its resistance to antifungal drugs.