1,531 research outputs found
Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk
According to the prevailing ‘clock’ model, chromosome decondensation and nuclear envelope reformation when cells exit mitosis are byproducts of Cdk1 inactivation at the metaphase-anaphase transition, controlled by the spindle assembly checkpoint. However, mitotic exit was recently shown to be a function of chromosome separation during anaphase, assisted by a midzone Aurora B phosphorylation gradient-the ‘ruler’ model. Here we found that Cdk1 remains active during anaphase due to ongoing APC/CCdc20- and APC/CCdh1-mediated degradation of B-type Cyclins in Drosophila and human cells. Failure to degrade B-type Cyclins during anaphase prevented mitotic exit in a Cdk1-dependent manner. Cyclin B1-Cdk1 localized at the spindle midzone in an Aurora B-dependent manner, with incompletely separated chromosomes showing the highest Cdk1 activity. Slowing down anaphase chromosome motion delayed Cyclin B1 degradation and mitotic exit in an Aurora B-dependent manner. Thus, a crosstalk between molecular ‘rulers’ and ‘clocks’ licenses mitotic exit only after proper chromosome separation.We thank Eric Griffis, Jean-René Huynh, Claudio Sunkel, Jonathon Pines, Melina Schuh and Christian Lehner for the kind gift of reagents, and Marco Gonzalez-Gaitán for supporting OA during the final stages of this work. LPC is the recipient of a Marie Skłodowska-Curie Action fellowship (grant agreement 746515). EMS holds an FCT Investigator position and his work is supported by Fundac¸ ão para a Ciência e a Tecnologia (PTDC/BEX-BCM/0432/2014). This work was supported by R01GM107026 grant to TJM and a Commonwealth Honors College grant to CMC Confocal and FLIM microscopy data collection was performed in the Light Microscopy Facility and Nikon Center of Excellence at the Institute for Applied Life Sciences, University of Massachusetts Amherst with support from the Massachusetts Life Science Center. Work in the HM lab is supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 681443) and FLAD Life Science 2020
Spectral plots and the representation and interpretation of biological data
It is basic question in biology and other fields to identify the char-
acteristic properties that on one hand are shared by structures from a
particular realm, like gene regulation, protein-protein interaction or neu- ral
networks or foodwebs, and that on the other hand distinguish them from other
structures. We introduce and apply a general method, based on the spectrum of
the normalized graph Laplacian, that yields repre- sentations, the spectral
plots, that allow us to find and visualize such properties systematically. We
present such visualizations for a wide range of biological networks and compare
them with those for networks derived from theoretical schemes. The differences
that we find are quite striking and suggest that the search for universal
properties of biological networks should be complemented by an understanding of
more specific features of biological organization principles at different
scales.Comment: 15 pages, 7 figure
Colored Motifs Reveal Computational Building Blocks in the C. elegans Brain
Background: Complex networks can often be decomposed into less complex sub-networks whose structures can give hints about the functional
organization of the network as a whole. However, these structural
motifs can only tell one part of the functional story because in this
analysis each node and edge is treated on an equal footing. In real
networks, two motifs that are topologically identical but whose nodes
perform very different functions will play very different roles in the
network.
Methodology/Principal Findings: Here, we combine structural information
derived from the topology of the neuronal network of the nematode C.
elegans with information about the biological function of these nodes,
thus coloring nodes by function. We discover that particular
colorations of motifs are significantly more abundant in the worm brain
than expected by chance, and have particular computational functions
that emphasize the feed-forward structure of information processing in
the network, while evading feedback loops. Interneurons are strongly
over-represented among the common motifs, supporting the notion that
these motifs process and transduce the information from the sensor
neurons towards the muscles. Some of the most common motifs identified
in the search for significant colored motifs play a crucial role in the
system of neurons controlling the worm's locomotion.
Conclusions/Significance: The analysis of complex networks in terms of
colored motifs combines two independent data sets to generate insight
about these networks that cannot be obtained with either data set
alone. The method is general and should allow a decomposition of any
complex networks into its functional (rather than topological) motifs
as long as both wiring and functional information is available
Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy
Next-generation radio surveys are about to transform radio astronomy by
discovering and studying tens of millions of previously unknown radio sources.
These surveys will provide new insights to understand the evolution of
galaxies, measuring the evolution of the cosmic star formation rate, and
rivalling traditional techniques in the measurement of fundamental cosmological
parameters. By observing a new volume of observational parameter space, they
are also likely to discover unexpected new phenomena. This review traces the
evolution of extragalactic radio continuum surveys from the earliest days of
radio astronomy to the present, and identifies the challenges that must be
overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201
Quantifying the Dynamics of Coupled Networks of Switches and Oscillators
Complex network dynamics have been analyzed with models of systems of coupled switches or systems of coupled oscillators. However, many complex systems are composed of components with diverse dynamics whose interactions drive the system's evolution. We, therefore, introduce a new modeling framework that describes the dynamics of networks composed of both oscillators and switches. Both oscillator synchronization and switch stability are preserved in these heterogeneous, coupled networks. Furthermore, this model recapitulates the qualitative dynamics for the yeast cell cycle consistent with the hypothesized dynamics resulting from decomposition of the regulatory network into dynamic motifs. Introducing feedback into the cell-cycle network induces qualitative dynamics analogous to limitless replicative potential that is a hallmark of cancer. As a result, the proposed model of switch and oscillator coupling provides the ability to incorporate mechanisms that underlie the synchronized stimulus response ubiquitous in biochemical systems
Urine culture doubtful in determining etiology of diffuse symptoms among elderly individuals: a cross-sectional study of 32 nursing homes
Background: The high prevalence of bacteriuria in elderly individuals makes it difficult to know if a new symptom is related to bacteria in the urine. There are different views concerning this relationship and bacteriuria often leads to antibiotic treatments. The aim of this study was to investigate the relationship between bacteria in the urine and new or increased restlessness, fatigue, confusion, aggressiveness, not being herself/himself, dysuria, urgency and fever in individuals at nursing homes for elderly when statistically considering the high prevalence of asymptomatic bacteriuria in this population.\ud
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Methods: In this cross-sectional study symptoms were registered and voided urine specimens were collected for urinary cultures from 651 elderly individuals. Logistic regressions were performed to evaluate the statistical correlation between bacteriuria and presence of a symptom at group level. To estimate the clinical relevance of statistical correlations at group level positive and negative etiological predictive values (EPV) were calculated.\ud
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Results: Logistic regression indicated some correlations at group level. Aside from Escherichia coli in the urine and not being herself/himself existing at least one month, but less than three months, EPV indicated no clinically useful correlation between any symptoms in this study and findings of bacteriuria.\ud
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Conclusions: Urinary cultures provide little or no useful information when evaluating diffuse symptoms among elderly residents of nursing homes. Either common urinary tract pathogens are irrelevant, or urine culture is an inappropriate test
Immunolocalization of Influenza A Virus and Markers of Inflammation in the Human Parkinson's Disease Brain
Although much is known regarding the molecular mechanisms leading to neuronal cell loss in Parkinson's disease (PD), the initiating event has not been identified. Prevailing theories including a chemical insult or infectious agent have been postulated as possible triggers, leading to neuroinflammation. We present immunohistochemical data indicating the presence of influenza A virus within the substantia nigra pars compacta (SNpc) from postmortem PD brain sections. Influenza A virus labeling was identified within neuromelanin granules as well as on tissue macrophages in the SNpc. Further supporting a role for neuroinflammation in PD was the identification of T-lymphocytes that colocalized with an antibody to caspase-cleaved Beclin-1 within the SNpc. The presence of influenza A virus together with macrophages and T-lymphocytes may contribute to the neuroinflammation associated with this disease
Thrombospondin-1 in Early Flow-Related Remodeling of Mesenteric Arteries from Young Normotensive and Spontaneously Hypertensive Rats
We tested the hypotheses that TSP-1 participates in the initiation of remodeling of small muscular arteries in response to altered blood flow and that the N-terminal domain of TSP-1 (hepI) can reverse the pathological inward remodeling of resistance arteries from SHR
Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar
We study the process with
initial-state-radiation events produced at the PEP-II asymmetric-energy
collider. The data were recorded with the BaBar detector at center-of-mass
energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454
. We investigate the mass
distribution in the region from 3.5 to 5.5 . Below 3.7
the signal dominates, and above 4
there is a significant peak due to the Y(4260). A fit to
the data in the range 3.74 -- 5.50 yields a mass value
(stat) (syst) and a width value (stat)(syst) for this state. We do not
confirm the report from the Belle collaboration of a broad structure at 4.01
. In addition, we investigate the system
which results from Y(4260) decay
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