bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of the germinal epithelium and early folliculogenesis during ovarian morphogenesis in the cichlid fish Cichlasoma dimerus (Teleostei, Perciformes)
Authors: Meijide Fernando J. , Rey Vázquez Graciela , Grier Harry J. , Lo Nostro Fabiana L. , Guerrero Graciela A. 
Published: October 2014

AbstractFormation of the germinal epithelium and folliculogenesis during ovarian development in Cichlasoma dimerus were described at the light‐ and electron‐microscopic levels. Prior to gonadal differentiation, germ cells and enveloping support cells reside within an inpocketing of the coelomic epithelium. Separation of the germinal and interstitial compartments of the gonad by a basement membrane is apparent from early gonadal development. Upon ovarian differentiation, oogonia undergo cyst‐forming divisions leading to the formation of clusters of interconnected cystocytes that synchronously enter meiosis, becoming oocytes. At the pachytene step, each oocyte becomes individualized by cytoplasmic extensions of prefollicle cells, thereby developing as an ovarian follicle. Subsequent somatic reorganization leads to the formation of the ovarian lumen in a cephalo‐caudal gradient. As a result, the germinal epithelium becomes internalized and lines the ovarian lumen. As defined by its origin from the germinal epithelium, the ovarian follicle is composed of an oocyte and the surrounding follicle cells. Thecal cells derived from the stroma encompass the basement membrane outside the follicle, thus forming a follicle complex. A common basement membrane is shared by the germinal epithelium and the follicle complex along a small portion of its surface. This point of attachment represents the site at which the oocyte would be released to the ovarian lumen during ovulation.
Novel antibodies directed against the human erythropoietin receptor: creating a basis for clinical implementation
Authors: Maxwell Perry , Melendez‐Rodríguez Florinda , Matchett Kyle B. , Aragones Julian , Ben‐Califa Nathalie , Jaekel Heidelinde , Hengst Ludger , Lindner Herbert , Bernardini Andre , Brockmeier Ulf , Fandrey Joachim , Grunert Fritz , Oster Howard S. , Mittelman Moshe , El‐Tanani Mohamed , Thiersch Markus , Schneider Gasser Edith M. , Gassmann Max , Dangoor David , Cuthbert Robert J. , Irvine Alexandra , Jordan Anne , Lappin Terence , Thompson John , Neumann Drorit 
Published: October 2014

SummaryRecombinant human erythropoietin (rHuEPO) is an effective treatment for anaemia but concerns that it causes disease progression in cancer patients by activation of EPO receptors (EPOR) in tumour tissue have been controversial and have restricted its clinical use. Initial clinical studies were flawed because they used polyclonal antibodies, later shown to lack specificity for EPOR. Moreover, multiple isoforms of EPOR caused by differential splicing have been reported in cancer cell lines at the mRNA level but investigations of these variants and their potential impact on tumour progression, have been hampered by lack of suitable antibodies. The EpoCan consortium seeks to promote improved pathological testing of EPOR, leading to safer clinical use of rHuEPO, by producing well characterized EPOR antibodies. Using novel genetic and traditional peptide immunization protocols, we have produced mouse and rat monoclonal antibodies, and show that several of these specifically recognize EPOR by Western blot, immunoprecipitation, immunofluorescence, flow cytometry and immunohistochemistry in cell lines and clinical material. Widespread availability of these antibodies should enable the research community to gain a better understanding of the role of EPOR in cancer, and eventually to distinguish patients who can be treated safely by rHuEPO from those at increased risk from treatment.
Wrong blood in tube – potential for serious outcomes: can it be prevented?
Authors: Bolton‐Maggs Paula H. B. , Wood Erica M. , Wiersum‐Osselton Johanna C. 
Published: October 2014

Summary‘Wrong blood in tube’ (WBIT) errors, where the blood in the tube is not that of the patient identified on the label, may lead to catastrophic outcomes, such as death from ABO‐incompatible red cell transfusion. Transfusion is a multistep, multidisciplinary process in which the human error rate has remained unchanged despite multiple interventions (education, training, competency testing and guidelines). The most effective interventions are probably the introduction of end‐to‐end electronic systems and a group‐check sample for patients about to receive their first transfusion, but neither of these eradicates all errors. Further longer term studies are required with assessment before and after introduction of the intervention. Although most focus has been on WBIT in relation to blood transfusion, all pathology samples should be identified and linked to the correct patient with the same degree of care. Human factors education and training could help to increase awareness of human vulnerability to error, particularly in the medical setting where there are many risk factors.
Incidence and risk factors for cataract after haematopoietic stem cell transplantation for childhood leukaemia: an LEA study
Authors: Horwitz Meryl , Auquier Pascal , Barlogis Vincent , Contet Audrey , Poiree Maryline , Kanold Justyna , Bertrand Yves , Plantaz Dominique , Galambrun Claire , Berbis Julie , Villes Virginie , Chastagner Pascal , Sirvent Nicolas , Oudin Claire , Michel Gérard 
Published: October 2014

SummaryCataract was prospectively assessed by serial slip lamp tests in 271 patients included in the Leucémie Enfants Adolescents (LEA) programme, the French cohort of childhood leukaemia survivors. All had received haematopoietic stem cell transplantation (HSCT) after total body irradiation (TBI, n = 201) or busulfan‐based (n = 70) myeloablative conditioning regimen. TBI was fractionated in all but six patients. The mean duration of follow‐up from HSCT was 10·3 years. Cataract was observed in 113/271 patients (41·7%); 9/113 (8·1%) needed surgery. Cumulative incidence after TBI increased over time from 30% at 5 years to 70·8% and 78% at 15 and 20 years, respectively, without any plateau thereafter. The 15‐year cumulative incidence was 12·5% in the Busulfan group. A higher cumulative steroid dose appeared to be a cofactor of TBI for cataract risk, in both univariate and multivariate Cox analysis. In the multivariate analysis, cataract had an impact in two quality of life domains: ‘the role limitation due to physical problems’ and ‘the role limitation due to emotional problems’. These data suggest that with increasing follow‐up, nearly all patients who receive TBI, even when fractionated, will suffer from cataract that can impact on their quality of life and that high cumulative steroid dose is a cofactor.
‘My great hope in life is to have a house, a family and a daughter’: relationships and sexuality in intellectually disabled people
Authors: Rojas Susana , Haya Ignacio , Lázaro‐Visa Susana 
Published: October 2014

Accessible summary

Relationships and sexuality are important for disabled people.

Through the voices of 16 intellectually disabled adults, this paper shows what they consider to be important in areas such as education or personal relationships.

Most of the people interviewed would like to have a partner and live together as a couple.

Intellectually disabled people encounter many barriers to obtain certain basic rights.

SummaryThis study starts from the premise that we are sexual beings, and therefore, sexuality is part of our lives and defines us as human beings. This is also true with regard to intellectually disabled people. Within the framework of broader qualitative research carried out in Spain, some partial results of an ongoing study aimed at finding out what a group of adults see as important in different areas of their lives are presented here. Through the personal narratives of 16 intellectually disabled people, this paper explores some of their ideas and demands about sexuality and their sexual lives. Most of the people interviewed expressed their desire to have a partner and to live as a couple. There is no doubt that many intellectually disabled people have greater control over their lives and the decisions that affect them, but as they tell us, the presence of old ideas can hinder them from securing their fundamental rights.
Repurposing Human PDE4 Inhibitors for Neglected Tropical Diseases. Evaluation of Analogs of the Human PDE4 Inhibitor GSK‐256066 as Inhibitors of PDEB1 of Trypanosoma brucei
Authors: Ochiana Stefan O. , Bland Nicholas D. , Settimo Luca , Campbell Robert K. , Pollastri Michael P. 
Published: October 2014

Cyclic nucleotide phosphodiesterases (PDEs) have been identified as important enzyme targets for drug development in both humans and Trypanosoma brucei, the causative agent of human African trypanosomiasis. With this in mind, we recently reported the profiling of a range of human phosphodiesterase inhibitors, showing that human PDE4 inhibitors tend to display the best potency against the trypanosomal phosphodiesterase TbrPDEB1. Among these was GSK‐256066, a potent inhibitor of human PDE4 and a weak inhibitor of TbrPDEB1. In this report, we describe the results of a structure–activity relationship study of this chemotype, leading to the discovery of analogs with improved potency against TbrPDEB1 and micromolar inhibition of T. brucei cellular growth. We rationalize the potency trends via molecular docking of the new inhibitors into a recently reported apo structure of TbrPDEB1. The studies in this article will inform future efforts in repurposing human PDE inhibitors as antitrypanosomal agents.
Impact of human maxillary sinus volume on grafts dimensional changes used in maxillary sinus augmentation: a multislice tomographic study
Authors: Favato Mário N. , Vidigal Bruno C.L. , Cosso Maurício G. , Manzi Flávio R. , Shibli Jamil A. , Zenóbio Elton G. 
Published: October 2014

AbstractPurposeTo assess the influence of complete maxillary sinus volume on the dimensional changes of different grafts used in maxillary sinus lift.Materials and MethodsAnalysis of 50 surgical procedures of maxillary sinus lift performed on 43 subjects using different grafting materials: fresh frozen allogenic particulated bone (11), hydroxyapatite (Endobon®) (17), 60% hydroxyapatite + 40% beta‐tricalcium phosphate (Bone Ceramic®) (12) and Bone Ceramic® + Emdogain® (10). One hundred and fifty multislice tomographic images of the maxillary sinus were obtained using the software Syngo CT 2011 A VOLUME, measuring complete maxillary sinus volume (T0) and dimensional changes of different graft materials during periods of 15 days (T1) and 180 days (T2). The factor studied was the influence of maxillary sinus volume on the dimensional changes of different graft materials used in maxillary sinus lift in patients with posterior edentulism. Data obtained were assessed using the Student's t‐test and Pearson's correlation coefficient.ResultsNo correlation (r 0.112) between the total maxillary sinus volume and the dimensional changes of the different graft materials used in this study was observed (P > 0.05).ConclusionThis study demonstrated that there is no sufficient evidence to support the thesis that the volume of the maxillary sinus influences the contraction of the grafts, at least on sample or the biomaterials evaluated in this cohort study.
Hb Wilde and Hb Patagonia: two novel elongated beta‐globin variants causing dominant beta‐thalassemia
Authors: Scheps Karen G. , Hasenahuer Marcia A. , Parisi Gustavo , Fornasari María S. , Pennesi Sandra P. , Erramouspe Beatriz , Basack Felisa N. , Veber Ernesto S. , Aversa Luis , Elena Graciela , Varela Viviana 
Published: October 2014

AbstractWe describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant β‐thalassemia‐like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the deletion of the third base of the codon 89 (T) and the codon 90 (GAG), whereas in Hb Patagonia, HBB:c.296_297dupGT(p.Asp99Trpfs*59), the frameshift mutation was due to a duplication of a ‘GT’ dinucleotide after the second base of codon 98 (GTG). The Hb Patagonia and Hb Wilde mutations would result in elongated β‐globin chains with modified C‐terminal sequences and a total of 155 and 157 amino acids residues, respectively. Based on bioinformatics and structural analysis, as well as protein modeling, we predict that the elongated β‐globins would affect the formation of the αβ dimers and their stability, which would further support the mechanism for the observed clinical features in both patients.
High level of full‐length cereblon mRNA in lower risk myelodysplastic syndrome with isolated 5q deletion is implicated in the efficacy of lenalidomide
Authors: Jonasova Anna , Bokorova Radka , Polak Jaroslav , Vostry Martin , Kostecka Arnost , Hajkova Hana , Neuwirtova Radana , Siskova Magda , Sponerova Dana , Cermak Jaroslav , Mikulenkova Dana , Cervinek Libor , Brezinova Jana , Michalova Kyra , Fuchs Ota 
Published: October 2014

AbstractDownregulation of cereblon (CRBN) gene expression is associated with resistance to the immunomodulatory drug lenalidomide and poor survival outcomes in multiple myeloma (MM) patients. However, the importance of CRBN gene expression in patients with myelodysplastic syndrome (MDS) and its impact on lenalidomide therapy are not clear. In this study, we evaluate cereblon expression in mononuclear cells isolated from bone marrow [23 lower risk MDS patients with isolated 5q deletion (5q‐), 37 lower risk MDS patients with chromosome 5 without the deletion of long arms (non‐5q‐), and 24 healthy controls] and from peripheral blood (38 patients with 5q‐, 52 non‐5q‐ patients and 25 healthy controls) to gain insight into, firstly, the role of cereblon in lower risk MDS patients with or without 5q deletion and, secondly, into the mechanisms of lenalidomide action. Patients with 5q‐ lower risk MDS have the highest levels of CRBN mRNA in comparison with both lower risk MDS without the deletion of long arms of chromosome 5 and healthy controls. CRBN gene expression was measured using the quantitative TaqMan real‐time PCR. High levels of CRBN mRNA were detected in all lenalidomide responders during the course of therapy. A significant decrease of the CRBN mRNA level during lenalidomide treatment is associated with loss of response to treatment and disease progression. These results suggest that, similar to the treatment of MM, high levels of full‐length CRBN mRNA in lower risk 5q‐ patients are necessary for the efficacy of lenalidomide.
Reduced sensitivity to both positive and negative reinforcement in mice over‐expressing the 5‐hydroxytryptamine transporter
Authors: Line Samantha J. , Barkus Chris , Rawlings Nancy , Jennings Katie , McHugh Stephen , Sharp Trevor , Bannerman David M. 
Published: October 2014

AbstractThe 5‐hydroxytryptamine (5‐HT) transporter (5‐HTT) is believed to play a key role in both normal and pathological psychological states. Much previous data suggest that the s allele of the polymorphic regulatory region of the 5‐HTT gene promoter is associated with reduced 5‐HTT expression and vulnerability to psychiatric disorders, including anxiety and depression. In comparison, the l allele, which increases 5‐HTT expression, is generally considered protective. However, recent data link this allele to both abnormal 5‐HT signalling and psychopathic traits. Here, we studied the processing of aversive and rewarding cues in transgenic mice that over‐express the 5‐HTT (5‐HTTOE mice). Compared with wild‐type mice, 5‐HTTOE mice froze less in response to both a tone that had previously been paired with footshock, and the conditioning context. In addition, on a decision‐making T‐maze task, 5‐HTTOE mice displayed reduced preference for a larger, delayed reward and increased preference for a smaller, immediate reward, suggesting increased impulsiveness compared with wild‐type mice. However, further inspection of the data revealed that 5‐HTTOE mice displayed a relative insensitivity to reward magnitude, irrespective of delay. In contrast, 5‐HTTOE mice appeared normal on tests of spatial working and reference memory, which required an absolute choice between options associated with either reward or no reward. Overall, the present findings suggest that 5‐HTT over‐expression results in a reduced sensitivity to both positive and negative reinforcers. Thus, these data show that increased 5‐HTT expression has some maladaptive effects, supporting recent suggestions that l allele homozygosity may be a potential risk factor for disabling psychiatric traits.
Amide hydrogen exchange in HIV–1 subtype B and C proteases – insights into reduced drug susceptibility and dimer stability
Authors: Naicker Previn , Stoychev Stoyan , Dirr Heini W. , Sayed Yasien 
Published: October 2014

Since its identification, HIV has continued to have a detrimental impact on the lives of millions of people throughout the world. The protease of HIV is a major target in antiviral treatment. The South African HIV–1 subtype C (C–SA) protease displays weaker binding affinity for some clinically approved protease inhibitors in comparison with the HIV–1 subtype B protease. The heavy HIV burden in sub‐Saharan Africa, where subtype C HIV–1 predominates, makes this disparity a topic of great interest. In light of this, the enzyme activity and affinity of protease inhibitors for the subtype B and C–SA proteases were determined. The relative vitality, indicating the selective advantage of polymorphisms, of the C–SA protease relative to the subtype B protease in the presence of ritonavir and darunavir was four‐ and tenfold greater, respectively. Dynamic differences that contribute to the reduced drug susceptibility of the C–SA protease were investigated by performing hydrogen–deuterium exchange/mass spectrometry (HDX/MS) on unbound subtype B and C–SA proteases. The reduced propensity to form the E35–R57 salt bridge, and alterations in the hydrophobic core of the C–SA protease, are proposed to affect the anchoring of the flexible flaps, resulting in an increased proportion of the fully open flap conformation. HDX/MS data suggested that the N–terminus of both proteases is less stable than the C–terminus of the proteases, thus explaining the increased efficacy of dimerization inhibitors targeted toward the C–terminus of HIV proteases. As far as we are aware, this is the first report on assessment of HIV protease dynamics using HDX/MS.
NLS copy‐number variation governs efficiency of nuclear import – case study on dUTPases
Authors: Róna Gergely , Pálinkás Hajnalka L. , Borsos Máté , Horváth András , Scheer Ildikó , Benedek András , Nagy Gergely N. , Zagyva Imre , Vértessy Beáta G. 
Published: October 2014

Nucleocytoplasmic trafficking of large macromolecules requires an active transport machinery. In many cases, this is initiated by binding of the nuclear localization signal (NLS) peptide of cargo proteins to importin‐α molecules. Fine orchestration of nucleocytoplasmic trafficking is of particularly high importance for proteins involved in maintenance of genome integrity, such as dUTPases, which are responsible for prevention of uracil incorporation into the genome. In most eukaryotes, dUTPases have two homotrimeric isoforms: one of these contains three NLSs and is present in the cell nucleus, while the other is located in the cytoplasm or the mitochondria. Here we focus on the unusual occurrence of a pseudo‐heterotrimeric dUTPase in Drosophila virilis that contains one NLS, and investigate its localization pattern compared to the homotrimeric dUTPase isoforms of Drosophila melanogaster. Although the interaction of individual NLSs with importin‐α has been well characterized, the question of how multiple NLSs of oligomeric cargo proteins affect their trafficking has been less frequently addressed in adequate detail. Using the D. virilis dUTPase as a fully relevant physiologically occurring model protein, we show that NLS copy number influences the efficiency of nuclear import in both insect and mammalian cell lines, as well as in D. melanogaster and D. virilis tissues. Biophysical data indicate that NLS copy number determines the stoichiometry of complexation between importin‐α and dUTPases. The main conclusion of our study is that, in D. virilis, a single dUTPase isoform efficiently reproduces the cellular dUTPase distribution pattern that requires two isoforms in D. melanogaster.Structured digital abstract• ABC dUTPase and importin-a bind by molecular sieving (View interaction) • AAA dUTPase and importin-a bind by molecular sieving (View interaction) • ABC dUTPase and importin-a bind by comigration in non denaturing gel electrophoresis (View interaction) • AAA dUTPase and importin-a bind by comigration in non denaturing gel electrophoresis (View interaction) • ABC dUTPase and importin-a bind by isothermal titration calorimetry (View interaction)&#x2022; AAA dUTPase and importin-a bind by isothermal titration calorimetry (View interaction)
Effects of adding acetic acid and molasses on fermentation quality and aerobic stability of total mixed ration silage prepared with hulless barley straw in Tibet
Authors: Qiu Xiaoyan , Guo Gang , Yuan Xianjun , Shao Tao 
Published: October 2014

AbstractIn order to enlarge the feed resources in Tibet, hulless barley (Hordeum vulgare L.) straw was conserved as total mixed ration (TMR) silage by combining it with whole crop oat (Avena sativa L.), alfalfa (Medicago sativa L.) and concentrate. This experiment was carried out to study the effects of acetic acid or/and molasses on the quality of TMR silages prepared with hulless barley straw. Treatments included: control (C) silage without additive, or silage with acetic acid (A, 0.3% fresh matter basis), molasses (M, 3% fresh matter basis) and A+M. Triplicate silos were opened after 45 days of ensiling and chemical and microbial analyses were conducted on the samples. Aerobic stability was tested 2, 4 and 6 days after exposure to air. Silages of all four TMR treatments were of good quality with high lactic acid (LA) concentration and low ratios of ammonia nitrogen in total nitrogen and butyric acid contents. Both the M and A+M silages had higher concentrations of LA (P < 0.05) and lower pH (P < 0.05) than the C and A silages. During aerobic exposure, aerobic deterioration occurred in the C and M silages with air infiltration. Resistance to deterioration was sustained in the A and A+M silages, with high concentration of acetic acid and low population (~4 log cfu g−1) of yeast throughout the 6‐day test. Furthermore, the A+M treatment showed a slow change in pH and LA in comparison to the A treatment. These findings indicate that adding acetic acid inhibited the yeast growth and improved the aerobic stability. The present study suggested that A+M addition was effective for improving both the fermentation quality and the aerobic stability of TMR silages containing hulless barley straw.