Ubiquitin sets the timer: impacts on aging and longevity

Protein homeostasis is essential for cellular function, organismal growth and viability. Damaged and aggregated proteins are turned over by two major proteolytic routes of the cellular quality-control pathways: the ubiquitin-proteasome system and autophagy. For both these pathways, ubiquitination provides the recognition signal for substrate selection. This Commentary discusses how ubiquitin-dependent proteolytic pathways are coordinated with stress- and aging-induced signals

A robust tracking system for low frame rate video

Tracking in low frame rate (LFR) videos is one of the most important problems in the tracking literature. Most existing approaches treat LFR video tracking as an abrupt motion tracking problem. However, in LFR video tracking applications, LFR not only causes abrupt motions, but also large appearance changes of objects because the objects’ poses and the illumination may undergo large changes from one frame to the next. This adds extra difficulties to LFR video tracking. In this paper, we propose a robust and general tracking system for LFR videos. The tracking system consists of four major parts: dominant color-spatial based object representation, bin-ratio based similarity measure, annealed particle swarm optimization (PSO) based searching, and an integral image based parameter calculation. The first two parts are combined to provide a good solution to the appearance changes, and the abrupt motion is effectively captured by the annealed PSO based searching. Moreover, an integral image of model parameters is constructed, which provides a look-up table for parameters calculation. This greatly reduces the computational load. Experimental results demonstrate that the proposed tracking system can effectively tackle the difficulties caused by LFR

Identification of Distinctive Patterns of USP19-Mediated Growth Regulation in Normal and Malignant Cells

We previously reported that the USP19 deubiquitinating enzyme positively regulates proliferation in fibroblasts by stabilizing KPC1, a ubiquitin ligase for p27Kip1. To explore whether this role of USP19 extends to other cellular systems, we tested the effects of silencing of USP19 in several human prostate and breast models, including carcinoma cell lines. Depletion of USP19 inhibited proliferation in prostate cancer DU145, PC-3 and 22RV1 cells, which was similar to the pattern established in fibroblasts in that it was due to decreased progression from G1 to S phase and associated with a stabilization of the cyclin-dependent kinase inhibitor p27Kip1. However, in contrast to previous findings in fibroblasts, the stabilization of p27Kip1 upon USP19 depletion was not associated with changes in the levels of the KPC1 ligase. USP19 could also regulate the growth of immortalized MCF10A breast epithelial cells through a similar mechanism. This regulatory pattern was lost, though, in breast cancer MCF7 and MDA-MB-231 cells and in prostate carcinoma LNCaP cells. Of interest, the transformation of fibroblasts through overexpression of an oncogenic form of Ras disrupted the USP19-mediated regulation of cell growth and of levels of p27Kip1 and KPC1. Thus, the cell context appears determinant for the ability of USP19 to regulate cell proliferation and p27Kip1 levels. This may occur through both KPC1 dependent and independent mechanisms. Moreover, a complete loss of USP19 function on cell growth may arise as a result of oncogenic transformation of cells

Paradoxical expression of cell cycle inhibitor p27 in endometrioid adenocarcinoma of the uterine corpus – correlation with proliferation and clinicopathological parameters

p27 is regarded as a cyclin-dependent kinase inhibitor of the G1-to-S cell cycle progression by suppressing the kinase activity of cyclin/cyclin-dependent kinase complex. This study aimed to investigate p27 expression in the normal endometrium and endometrioid adenocarcinoma of the uterine corpus and the correlation of its expression with cell proliferation and clinicopathological parameters. Tissue samples of 127 endometrioid adenocarcinomas and 15 normal endometria were used in the study. Immunohistochemical staining for detecting p27 and Ki-67 was performed by the labelled streptavidin-biotin method on formalin-fixed and paraffin-embedded tissue samples. The expression was given as the labelling index, which indicates the percentage of positive nuclei. p27 staining was observed in the nuclei of the glandular cells in the functional layer of the secretory phase endometrium, whereas it was negative in those of the proliferative phase. In endometrioid adenocarcinomas, the labelling index of p27 expression paradoxically increased more significantly in the higher histological grades and was correlated with that of Ki-67. The high level of p27 expression was associated with clinicopathological parameters such as FIGO stage, lymph node metastasis, lymphovascular space involvement and myometrial invasion. High p27 expression was linked to higher grades of endometrioid adenocarcinoma, cell proliferation and some clinical prognostic factors. These results indicate that p27 might be an indicator of poor prognosis

Siderophore production by Bacillus megaterium : effect of growth-phase and cultural conditions

Siderophore production by Bacillus megaterium was detected, in an iron-deficient culture medium, during the exponential growth phase, prior to the sporulation, in the presence of glucose; these results suggested that the onset of siderophore production did not require glucose depletion and was not related with the sporulation. The siderophore production by B. megaterium was affected by the carbon source used. The growth on glycerol promoted the very high siderophore production (1,182 μmol g−1 dry weight biomass); the opposite effect was observed in the presence of mannose (251 μmol g−1 dry weight biomass). The growth in the presence of fructose, galactose, glucose, lactose, maltose or sucrose, originated similar concentrations of siderophore (546–842 μmol g−1 dry weight biomass). Aeration had a positive effect on the production of siderophore. Incubation of B. megaterium under static conditions delayed and reduced the growth and the production of siderophore, compared with the incubation in stirred conditions.The authors thank Porto University/Totta Bank for their financial support through the project "Microbiological production of chelating agents" (Ref: 180). The authors also thank the Fundacao para a Ciencia e a Tecnologia (FCT) through the Portuguese Government for their financial support of this work through the grants Strategic project-LA23/2013-2014 (IBB) and PEST-C/EQB/LA0006/2011 (REQUIMTE). Manuela D. Machado gratefully acknowledges the postdoctoral (SFRH/BPD/72816/2010) grant from FCT

Cks1 Is Required for Tumor Cell Proliferation but Not Sufficient to Induce Hematopoietic Malignancies

The Cks1 component of the SCFSkp2 complex is necessary for p27Kip1 ubiquitylation and degradation. Cks1 expression is elevated in various B cell malignancies including Burkitt lymphoma and multiple myeloma. We have previously shown that loss of Cks1 results in elevated p27Kip1 levels and delayed tumor development in a mouse model of Myc-induced B cell lymphoma. Surprisingly, loss of Skp2 in the same mouse model also resulted in elevated p27Kip1 levels but exhibited no impact on tumor onset. This raises the possibility that Cks1 could have other oncogenic activities than suppressing p27Kip1. To challenge this notion we have targeted overexpression of Cks1 to B cells using a conditional retroviral bone marrow transduction-transplantation system. Despite potent ectopic overexpression, Cks1 was unable to promote B cell hyperproliferation or B cell malignancies, indicating that Cks1 is not oncogenic when overexpressed in B cells. Since Skp2 overexpression can drive T-cell tumorigenesis or other cancers we also widened the quest for oncogenic activity of Cks1 by ubiquitously expressing Cks1 in hematopoetic progenitors. At variance with c-Myc overexpression, which caused acute myeloid leukemia, Cks1 overexpression did not induce myeloproliferation or leukemia. Therefore, despite being associated with a poor prognosis in various malignancies, sole Cks1 expression is insufficient to induce lymphoma or a myeloproliferative disease in vivo

On the Size and Flight Diversity of Giant Pterosaurs, the Use of Birds as Pterosaur Analogues and Comments on Pterosaur Flightlessness

The size and flight mechanics of giant pterosaurs have received considerable research interest for the last century but are confused by conflicting interpretations of pterosaur biology and flight capabilities. Avian biomechanical parameters have often been applied to pterosaurs in such research but, due to considerable differences in avian and pterosaur anatomy, have lead to systematic errors interpreting pterosaur flight mechanics. Such assumptions have lead to assertions that giant pterosaurs were extremely lightweight to facilitate flight or, if more realistic masses are assumed, were flightless. Reappraisal of the proportions, scaling and morphology of giant pterosaur fossils suggests that bird and pterosaur wing structure, gross anatomy and launch kinematics are too different to be considered mechanically interchangeable. Conclusions assuming such interchangeability—including those indicating that giant pterosaurs were flightless—are found to be based on inaccurate and poorly supported assumptions of structural scaling and launch kinematics. Pterosaur bone strength and flap-gliding performance demonstrate that giant pterosaur anatomy was capable of generating sufficient lift and thrust for powered flight as well as resisting flight loading stresses. The retention of flight characteristics across giant pterosaur skeletons and their considerable robustness compared to similarly-massed terrestrial animals suggest that giant pterosaurs were not flightless. Moreover, the term ‘giant pterosaur’ includes at least two radically different forms with very distinct palaeoecological signatures and, accordingly, all but the most basic sweeping conclusions about giant pterosaur flight should be treated with caution. Reappraisal of giant pterosaur material also reveals that the size of the largest pterosaurs, previously suggested to have wingspans up to 13 m and masses up to 544 kg, have been overestimated. Scaling of fragmentary giant pterosaur remains have been misled by distorted fossils or used inappropriate scaling techniques, indicating that 10–11 m wingspans and masses of 200–250 kg are the most reliable upper estimates of known pterosaur size

The influence of speed and size on avian terrestrial locomotor biomechanics: predicting locomotion in extinct theropod dinosaurs

How extinct, non-avian theropod dinosaurs moved is a subject of considerable interest and controversy. A better understanding of non-avian theropod locomotion can be achieved by better understanding terrestrial locomotor biomechanics in their modern descendants, birds. Despite much research on the subject, avian terrestrial locomotion remains little explored in regards to how kinematic and kinetic factors vary together with speed and body size. Here, terrestrial locomotion was investigated in twelve species of ground-dwelling bird, spanning a 1,780-fold range in body mass, across almost their entire speed range. Particular attention was devoted to the ground reaction force (GRF), the force that the feet exert upon the ground. Comparable data for the only other extant obligate, striding biped, humans, were also collected and studied. In birds, all kinematic and kinetic parameters examined changed continuously with increasing speed, while in humans all but one of those same parameters changed abruptly at the walk-run transition. This result supports previous studies that show birds to have a highly continuous locomotor repertoire compared to humans, where discrete ‘walking’ and ‘running’ gaits are not easily distinguished based on kinematic patterns alone. The influences of speed and body size on kinematic and kinetic factors in birds are developed into a set of predictive relationships that may be applied to extinct, non-avian theropods. The resulting predictive model is able to explain 79–93% of the observed variation in kinematics and 69–83% of the observed variation in GRFs, and also performs well in extrapolation tests. However, this study also found that the location of the whole-body centre of mass may exert an important influence on the nature of the GRF, and hence some caution is warranted, in lieu of further investigation

New Information on the Cranial Anatomy of Acrocanthosaurus atokensis and Its Implications for the Phylogeny of Allosauroidea (Dinosauria: Theropoda)

Allosauroidea has a contentious taxonomic and systematic history. Within this group of theropod dinosaurs, considerable debate has surrounded the phylogenetic position of the large-bodied allosauroid Acrocanthosaurus atokensis from the Lower Cretaceous Antlers Formation of North America. Several prior analyses recover Acrocanthosaurus atokensis as sister taxon to the smaller-bodied Allosaurus fragilis known from North America and Europe, and others nest Acrocanthosaurus atokensis within Carcharodontosauridae, a large-bodied group of allosauroids that attained a cosmopolitan distribution during the Early Cretaceous.Re-evaluation of a well-preserved skull of Acrocanthosaurus atokensis (NCSM 14345) provides new information regarding the palatal complex and inner surfaces of the skull and mandible. Previously inaccessible internal views and articular surfaces of nearly every element of the skull are described. Twenty-four new morphological characters are identified as variable in Allosauroidea, combined with 153 previously published characters, and evaluated for eighteen terminal taxa. Systematic analysis of this dataset recovers a single most parsimonious topology placing Acrocanthosaurus atokensis as a member of Allosauroidea, in agreement with several recent analyses that nest the taxon well within Carcharodontosauridae.A revised diagnosis of Acrocanthosaurus atokensis finds that the species is distinguished by four primary characters, including: presence of a knob on the lateral surangular shelf; enlarged posterior surangular foramen; supraoccipital protruding as a double-boss posterior to the nuchal crest; and pneumatic recess within the medial surface of the quadrate. Furthermore, the recovered phylogeny more closely agrees with the stratigraphic record than hypotheses that place Acrocanthosaurus atokensis as more closely related to Allosaurus fragilis. Fitch optimization of body size is also more consistent with the placement of Acrocanthosaurus atokensis within a clade of larger carcharodontosaurid taxa than with smaller-bodied taxa near the base of Allosauroidea. This placement of Acrocanthosaurus atokensis supports previous hypotheses of a global carcharodontosaurid radiation during the Early Cretaceous