117 research outputs found
The carboxypeptidase E knockout mouse exhibits endocrinological and behavioral deficits
A carboxypeptidase E (CPE) knockout ( KO) mouse was generated by deletion of exons 4 and 5 from the CPE gene, and its phenotype was characterized. KO mice became obese by 10 - 12 wk of age and reached 60 - 80 g by 40 wk. At this age, body fat content was more than double that in the wild-type (WT) controls. The null animals consumed more food overall, were less physically active during the light phase of the light-dark cycle, and burned fewer calories as fat than WT littermates. Fasting levels of glucose and insulin-like immunoreactivity in plasma were elevated in both male and female KO mice at approximately 20 wk; males recovered fully and females partially from this state by 32 wk. At this time, insulin-like immunoreactivity in the plasma, identified as proinsulin, was 50 - 100 times higher than that of the WT animals. The KO mice showed impaired glucose clearance and were insulin resistant. High levels of leptin and no circulating fully processed cocaine- and amphetamine-related transcript, a peptide that is responsive to leptin-induced feedback inhibition of feeding, were found in serum. The KO mice were subfertile and showed deficits in GnRH processing in the hypothalamus. Behavioral analyses revealed that KO animals showed diminished reactivity to stimuli and had reduced muscle strength and coordination, as well as visual placing and toe-pinch reflexes. These data demonstrate that CPE KO mice display a wide range of neural and endocrine abnormalities and suggest that CPE may have additional physiological roles beyond those ascribed to peptide processing and sorting of prohormones in cells
Incomplete posttranslational prohormone modifications in hyperactive neuroendocrine cells
Contains fulltext :
76028.pdf (publisher's version ) (Open Access)8 p
POMC: The Physiological Power of Hormone Processing.
Pro-opiomelanocortin (POMC) is the archetypal polypeptide precursor of hormones and neuropeptides. In this review, we examine the variability in the individual peptides produced in different tissues and the impact of the simultaneous presence of their precursors or fragments. We also discuss the problems inherent in accurately measuring which of the precursors and their derived peptides are present in biological samples. We address how not being able to measure all the combinations of precursors and fragments quantitatively has affected our understanding of the pathophysiology associated with POMC processing. To understand how different ratios of peptides arise, we describe the role of the pro-hormone convertases (PCs) and their tissue specificities and consider the cellular processing pathways which enable regulated secretion of different peptides that play crucial roles in integrating a range of vital physiological functions. In the pituitary, correct processing of POMC peptides is essential to maintain the hypothalamic-pituitary-adrenal axis, and this processing can be disrupted in POMC-expressing tumors. In hypothalamic neurons expressing POMC, abnormalities in processing critically impact on the regulation of appetite, energy homeostasis, and body composition. More work is needed to understand whether expression of the POMC gene in a tissue equates to release of bioactive peptides. We suggest that this comprehensive view of POMC processing, with a focus on gaining a better understanding of the combination of peptides produced and their relative bioactivity, is a necessity for all involved in studying this fascinating physiological regulatory phenomenon
Measurement of electron antineutrino oscillation based on 1230 days of operation of the Daya Bay experiment
published_or_final_versio
Improved Search for a Light Sterile Neutrino with the Full Configuration of the Daya Bay Experiment
published_or_final_versio
Improved measurement of the reactor antineutrino flux and spectrum at Daya Bay
published_or_final_versio
Limits on active to sterile neutrino oscillations from disappearance searches in the MINOS, Daya Bay, and bugey-3 experiments
Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti)neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on sin^2 2θμe are set over 6 orders of magnitude in the sterile mass-squared splitting Δm^2 41. The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for Δm^2 41 < 0.8 eV^2 at 95% CLs
Shedding Light on the Galaxy Luminosity Function
From as early as the 1930s, astronomers have tried to quantify the
statistical nature of the evolution and large-scale structure of galaxies by
studying their luminosity distribution as a function of redshift - known as the
galaxy luminosity function (LF). Accurately constructing the LF remains a
popular and yet tricky pursuit in modern observational cosmology where the
presence of observational selection effects due to e.g. detection thresholds in
apparent magnitude, colour, surface brightness or some combination thereof can
render any given galaxy survey incomplete and thus introduce bias into the LF.
Over the last seventy years there have been numerous sophisticated
statistical approaches devised to tackle these issues; all have advantages --
but not one is perfect. This review takes a broad historical look at the key
statistical tools that have been developed over this period, discussing their
relative merits and highlighting any significant extensions and modifications.
In addition, the more generalised methods that have emerged within the last few
years are examined. These methods propose a more rigorous statistical framework
within which to determine the LF compared to some of the more traditional
methods. I also look at how photometric redshift estimations are being
incorporated into the LF methodology as well as considering the construction of
bivariate LFs. Finally, I review the ongoing development of completeness
estimators which test some of the fundamental assumptions going into LF
estimators and can be powerful probes of any residual systematic effects
inherent magnitude-redshift data.Comment: 95 pages, 23 figures, 3 tables. Now published in The Astronomy &
Astrophysics Review. This version: bring in line with A&AR format
requirements, also minor typo corrections made, additional citations and
higher rez images adde
Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons
Ligaments and tendons are soft connective tissues which serve essential roles for biomechanical function of the musculoskeletal system by stabilizing and guiding the motion of diarthrodial joints. Nevertheless, these tissues are frequently injured due to repetition and overuse as well as quick cutting motions that involve acceleration and deceleration. These injuries often upset this balance between mobility and stability of the joint which causes damage to other soft tissues manifested as pain and other morbidity, such as osteoarthritis
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