118 research outputs found
Searching for network modules
When analyzing complex networks a key target is to uncover their modular
structure, which means searching for a family of modules, namely node subsets
spanning each a subnetwork more densely connected than the average. This work
proposes a novel type of objective function for graph clustering, in the form
of a multilinear polynomial whose coefficients are determined by network
topology. It may be thought of as a potential function, to be maximized, taking
its values on fuzzy clusterings or families of fuzzy subsets of nodes over
which every node distributes a unit membership. When suitably parametrized,
this potential is shown to attain its maximum when every node concentrates its
all unit membership on some module. The output thus is a partition, while the
original discrete optimization problem is turned into a continuous version
allowing to conceive alternative search strategies. The instance of the problem
being a pseudo-Boolean function assigning real-valued cluster scores to node
subsets, modularity maximization is employed to exemplify a so-called quadratic
form, in that the scores of singletons and pairs also fully determine the
scores of larger clusters, while the resulting multilinear polynomial potential
function has degree 2. After considering further quadratic instances, different
from modularity and obtained by interpreting network topology in alternative
manners, a greedy local-search strategy for the continuous framework is
analytically compared with an existing greedy agglomerative procedure for the
discrete case. Overlapping is finally discussed in terms of multiple runs, i.e.
several local searches with different initializations.Comment: 10 page
Variation of Basal EROD Activities in Ten Passerine Bird Species – Relationships with Diet and Migration Status
Inter-specific differences in animal defence mechanisms against toxic substances are currently poorly understood. The ethoxyresorufin-O-deethylase (EROD) enzyme plays an important role in defence against toxic chemicals in a wide variety of animals, and it is an important biomarker for environmental contamination. We compared basal hepatic EROD activity levels among ten passerine species to see if there is inter-specific variation in enzyme activity, especially in relation to their diet and migration status. Migratory insectivores showed higher EROD activity compared to granivores. We hypothesize that the variable invertebrate diet of migratory insectivores contains a wider range of natural toxins than the narrower diet of granivores. This may have affected the evolution of mixed function oxidases (MFO) system and enzyme activities. We further tested whether metabolic rates or relative liver size were associated with the variation in detoxification capacity. We found no association between EROD activity and relative (per mass unit) basal metabolic rate (BMR). Instead, EROD activity and relative liver mass (% of body mass) correlated positively, suggesting that a proportionally large liver also functions efficiently. Our results suggest that granivores and non-migratory birds may be more vulnerable to environmental contaminants than insectivores and migratory birds. The diet and migration status, however, are phylogenetically strongly connected to each other, and their roles cannot be fully separated in our analysis with only ten passerine species
Does true Gleason pattern 3 merit its cancer descriptor?
Nearly five decades following its conception, the Gleason grading system remains a cornerstone in the prognostication and management of patients with prostate cancer. In the past few years, a debate has been growing whether Gleason score 3 + 3 = 6 prostate cancer is a clinically significant disease. Clinical, molecular and genetic research is addressing the question whether well characterized Gleason score 3 + 3 = 6 disease has the ability to affect the morbidity and quality of life of an individual in whom it is diagnosed. The consequences of treatment of Gleason score 3 + 3 = 6 disease are considerable; few men get through their treatments without sustaining some harm. Further modification of the classification of prostate cancer and dropping the label cancer for Gleason score 3 + 3 = 6 disease might be warranted
Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis
Bronchiectasis is a disease associated with chronic progressive and irreversible dilatation of the bronchi and is characterised by chronic infection and associated inflammation. The prevalence of bronchiectasis is age-related and there is some geographical variation in incidence, prevalence and clinical features. Most bronchiectasis is reported to be idiopathic however post-infectious aetiologies dominate across Asia especially secondary to tuberculosis. Most focus to date has been on the study of airway bacteria, both as colonisers and causes of exacerbations. Modern molecular technologies including next generation sequencing (NGS) have become invaluable tools to identify microorganisms directly from sputum and which are difficult to culture using traditional agar based methods. These have provided important insight into our understanding of emerging pathogens in the airways of people with bronchiectasis and the geographical differences that occur. The contribution of the lung microbiome, its ethnic variation, and subsequent roles in disease progression and response to therapy across geographic regions warrant further investigation. This review summarises the known geographical differences in the aetiology, epidemiology and microbiology of bronchiectasis. Further, we highlight the opportunities offered by emerging molecular technologies such as -omics to further dissect out important ethnic differences in the prognosis and management of bronchiectasis.NMRC (Natl Medical Research Council, S’pore)MOH (Min. of Health, S’pore)Published versio
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field
The evolution of epigean and stygobitic species of Koonunga Sayce, 1907 (Syncarida: Anaspidacea) in Southern Australia, with the description of three new species
Three new species of Koonunga were discovered in surface and subterranean waters in southern Australia, and were defined using mtDNA analyses and morphology. The new species are: Koonunga hornei Leijs & King; K. tatiaraensis Leijs & King and K. allambiensis Leijs & King. Molecular clock analyses indicate that the divergence times of the species are older than the landscape that they currently inhabit. Different scenarios explaining this apparent discrepancy are discussed in the context of the palaeography of the area. A freshwater epigean origin for Koonunga is considered the most likely hypothesis, whereby some lineages made the transition to the subterranean environment within the last few million years influenced by significant climatic cooling/drying. We discuss the possibility that one stygobitic lineage secondarily regained some of its body pigmentation as adaptation to increased photic conditions after cave collapse and forming of cenotes during the last glacial maximum.Remko Leijs, Tessa Bradford, James G. Mitchell, William F. Humphreys, Steven J. B. Cooper, Peter Goonan, Rachael A. Kin
Omics-based molecular techniques in oral pathology centred cancer: Prospect and challenges in Africa
: The completion of the human genome project and the accomplished milestones in the human
proteome project; as well as the progress made so far in computational bioinformatics and “big data” processing have
contributed immensely to individualized/personalized medicine in the developed world.At the dawn of precision medicine, various omics-based therapies and bioengineering can now be
applied accurately for the diagnosis, prognosis, treatment, and risk stratifcation of cancer in a manner that was
hitherto not thought possible. The widespread introduction of genomics and other omics-based approaches into
the postgraduate training curriculum of diverse medical and dental specialties, including pathology has improved
the profciency of practitioners in the use of novel molecular signatures in patient management. In addition, intricate
details about disease disparity among diferent human populations are beginning to emerge. This would facilitate the
use of tailor-made novel theranostic methods based on emerging molecular evidences
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