GLORIA — GEOMAR Library Ocean Research Information Access

1

Unbekannt

Delayed Puberty but Normal Fertility in Mice With Selective Deletion of Insulin Receptors From Kiss1 Cells (2013)

Qiu, X., Dowling, A. R., Marino, J. S., Faulkner, L. D., Bryant, B., Bruning, J. C., Elias, C. F., Hill, J. W.

Oxford University Press

In: Endocrinology

zur Merkliste hinzufügen auf der Merkliste

Details

Publikationsdatum: 2013-02-22

Beschreibung: Pubertal onset only occurs in a favorable, anabolic hormonal environment. The neuropeptide kisspeptin, encoded by the Kiss1 gene, modifies GnRH neuronal activity to initiate puberty and maintain fertility, but the factors that regulate Kiss1 neurons and permit pubertal maturation remain to be clarified. The anabolic factor insulin may signal nutritional status to these neurons. To determine whether insulin sensing plays an important role in Kiss1 neuron function, we generated mice lacking insulin receptors in Kiss1 neurons (IR Kiss mice). IR Kiss females showed a delay in vaginal opening and in first estrus, whereas IR Kiss males also exhibited late sexual maturation. Correspondingly, LH levels in IR Kiss mice were reduced in early puberty in both sexes. Adult reproductive capacity, body weight, fat composition, food intake, and glucose regulation were comparable between the 2 groups. These data suggest that impaired insulin sensing by Kiss1 neurons delays the initiation of puberty but does not affect adult fertility. These studies provide insight into the mechanisms regulating pubertal timing in anabolic states.

Print ISSN: 0013-7227

Thema: Medizin

Publiziert von Oxford University Press im Namen von The Endocrine Society.

Permalink

	Standort	Signatur	Einschränkungen	Verfügbarkeit

Andere fanden auch interessant ...

PAPER CURRENT

Volltext

2

Unbekannt

Cardiomyocyte ryanodine receptor degradation by chaperone-mediated autophagy (2013)

Pedrozo, Z., Torrealba, N., Fernandez, C., Gatica, D., Toro, B., Quiroga, C., Rodriguez, A. E., Sanchez, G., Gillette, T. G., Hill, J. A., Donoso, P., Lavandero, S.

Oxford University Press

In: Cardiovascular Research

zur Merkliste hinzufügen auf der Merkliste

Details

Publikationsdatum: 2013-04-24

Beschreibung: Time for primary review: 15 days Aims Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing the sequence KFERQ. These proteins are targeted by chaperones and delivered to lysosomes where they are translocated into the lysosomal lumen and degraded via the lysosome-associated membrane protein type 2A (LAMP-2A). Mutations in LAMP2 that inhibit autophagy result in Danon disease characterized by hypertrophic cardiomyopathy. The ryanodine receptor type 2 (RyR2) plays a key role in cardiomyocyte excitation–contraction and its dysfunction can lead to cardiac failure. Whether RyR2 is degraded by CMA is unknown. Methods and results To induce CMA, cultured neonatal rat cardiomyocytes were treated with geldanamycin (GA) to promote protein degradation through this pathway. GA increased LAMP-2A levels together with its redistribution and colocalization with Hsc70 in the perinuclear region, changes indicative of CMA activation. The inhibition of lysosomes but not proteasomes prevented the loss of RyR2. The recovery of RyR2 content after incubation with GA by siRNA targeting LAMP-2A suggests that RyR2 is degraded via CMA. In silico analysis also revealed that the RyR2 sequence harbours six KFERQ motifs which are required for the recognition Hsc70 and its degradation via CMA. Our data suggest that presenilins are involved in RyR2 degradation by CMA. Conclusion These findings are consistent with a model in which oxidative damage of the RyR2 targets it for turnover by presenilins and CMA, which could lead to removal of damaged or leaky RyR2 channels.

Print ISSN: 0008-6363

Digitale ISSN: 1755-3245

Thema: Medizin

Publiziert von Oxford University Press

Permalink

	Standort	Signatur	Einschränkungen	Verfügbarkeit

Andere fanden auch interessant ...

PAPER CURRENT

Volltext

3

Unbekannt

Memoir: template-based structure prediction for membrane proteins (2013)

Ebejer, J.-P., Hill, J. R., Kelm, S., Shi, J., Deane, C. M.

Oxford University Press

In: Nucleic Acids Research

zur Merkliste hinzufügen auf der Merkliste

Details

Publikationsdatum: 2013-06-23

Beschreibung: Membrane proteins are estimated to be the targets of 50% of drugs that are currently in development, yet we have few membrane protein crystal structures. As a result, for a membrane protein of interest, the much-needed structural information usually comes from a homology model. Current homology modelling software is optimized for globular proteins, and ignores the constraints that the membrane is known to place on protein structure. Our Memoir server produces homology models using alignment and coordinate generation software that has been designed specifically for transmembrane proteins. Memoir is easy to use, with the only inputs being a structural template and the sequence that is to be modelled. We provide a video tutorial and a guide to assessing model quality. Supporting data aid manual refinement of the models. These data include a set of alternative conformations for each modelled loop, and a multiple sequence alignment that incorporates the query and template. Memoir works with both α-helical and β-barrel types of membrane proteins and is freely available at http://opig.stats.ox.ac.uk/webapps/memoir .

Print ISSN: 0305-1048

Digitale ISSN: 1362-4962

Thema: Biologie

Publiziert von Oxford University Press

Permalink

	Standort	Signatur	Einschränkungen	Verfügbarkeit

Andere fanden auch interessant ...

PAPER CURRENT

Volltext

4

Unbekannt

On the stationary distribution of iterative imputations (2014)

Liu, J., Gelman, A., Hill, J., Su, Y.-S., Kropko, J.

Oxford University Press

In: Biometrika

zur Merkliste hinzufügen auf der Merkliste

Details

Publikationsdatum: 2014-02-26

Beschreibung: Iterative imputation, in which variables are imputed one at a time conditional on all the others, is a popular technique that can be convenient and flexible, as it replaces a potentially difficult multivariate modelling problem with relatively simple univariate regressions. In this paper, we begin to characterize the stationary distributions of iterative imputations and their statistical properties, accounting for the conditional models being iteratively estimated from data rather than being prespecified. When the families of conditional models are compatible, we provide sufficient conditions under which the imputation distribution converges in total variation to the posterior distribution of a Bayesian model. When the conditional models are incompatible but valid, we show that the combined imputation estimator is consistent.

Print ISSN: 0006-3444

Digitale ISSN: 1464-3510

Thema: Biologie , Mathematik , Medizin

Publiziert von Oxford University Press

Permalink

	Standort	Signatur	Einschränkungen	Verfügbarkeit

Andere fanden auch interessant ...

PAPER CURRENT

Volltext

5

Unbekannt

MP-T: improving membrane protein alignment for structure prediction (2012)

Hill, J. R., Deane, C. M.

Oxford University Press

In: Bioinformatics

zur Merkliste hinzufügen auf der Merkliste

Details

Publikationsdatum: 2012-12-21

Beschreibung: Motivation: Membrane proteins are clinically relevant, yet their crystal structures are rare. Models of membrane proteins are typically built from template structures with low sequence identity to the target sequence, using a sequence-structure alignment as a blueprint. This alignment is usually made with programs designed for use on soluble proteins. Biological membranes have layers of varying hydrophobicity, and membrane proteins have different amino-acid substitution preferences from their soluble counterparts. Here we include these factors into an alignment method to improve alignments and consequently improve membrane protein models. Results: We developed Membrane Protein Threader (MP-T), a sequence-structure alignment tool for membrane proteins based on multiple sequence alignment. Alignment accuracy is tested against seven other alignment methods over 165 non-redundant alignments of membrane proteins. MP-T produces more accurate alignments than all other methods tested ( F M from +0.9 to +5.5%). Alignments generated by MP-T also lead to significantly better models than those of the best alternative alignment tool (one-fourth of models see an increase in GDT_TS of ≥4%). Availability: All source code, alignments and models are available at http://www.stats.ox.ac.uk/proteins/resources Contact: deane@stats.ox.ac.uk Supplementary information : Supplementary data are available at Bioinformatics online.

Print ISSN: 1367-4803

Digitale ISSN: 1460-2059

Thema: Biologie , Informatik , Medizin

Publiziert von Oxford University Press

Permalink

	Standort	Signatur	Einschränkungen	Verfügbarkeit

Andere fanden auch interessant ...

PAPER CURRENT

Volltext

6

Unbekannt

Commentary: Physical activity and weight control (2014)

Hill, J. O., Peters, J. C.

Oxford University Press

In: International Journal of Epidemiology

zur Merkliste hinzufügen auf der Merkliste

Details

Publikationsdatum: 2014-01-11

Print ISSN: 0300-5771

Digitale ISSN: 1464-3685

Thema: Medizin

Publiziert von Oxford University Press

Permalink

	Standort	Signatur	Einschränkungen	Verfügbarkeit

Andere fanden auch interessant ...

PAPER CURRENT

Volltext