IS METABOLOMICS THE DIAGNOSTIC TOOL FOR MEDICAL DIAGNOSTICS OF CANCER? AN EXAMPLE BASED ON LUNG AND BREAST CANCER

Background. Metabolomics is a relatively new diagnostic tool that allows a deep insight into the body metabolism at a cellular level. Objective. This paper provides a comprehensive view into the metabolomic methodology and shows usefulness of this approach in diagnosing and stratifying lung and breast cancers. Methods. Literature review of metabolomics studies and its clinical application in the diagnosis of cancer-selected studies. Results. In general, the metabolomic approach comprises three steps: 1) sampling and preparing biofluids or tissue homogenates, 2) identification of low-molecular weight compounds up to 1.0 kDa using nuclear magnetic resonance, mostly 1H-NMR and/or mass spectrometry, and finally 3) data processing and analysing. It is possible to identify a set of metabolites which is specific for a certain metabolic status (the metabolic fingerprint). Furthermore, this set of metabolites provides information of possible pathomechanisms involved in the disease process i.e. information about the disease etiology. It has been proven that the change in metabolome precedes other biomarkers of the disease; not only clinical symptoms but other laboratory findings as well. Consequently, this approach, if sufficiently validated, seems to be very promising especially in screening and early diagnosing. Conclusions. It was demonstrated that metabolomic approach allows to discriminate patients with cancer from healthy persons, as well as to differentiate between clinical stages of the cancer

Good Random Matrices over Finite Fields

The random matrix uniformly distributed over the set of all m-by-n matrices over a finite field plays an important role in many branches of information theory. In this paper a generalization of this random matrix, called k-good random matrices, is studied. It is shown that a k-good random m-by-n matrix with a distribution of minimum support size is uniformly distributed over a maximum-rank-distance (MRD) code of minimum rank distance min{m,n}-k+1, and vice versa. Further examples of k-good random matrices are derived from homogeneous weights on matrix modules. Several applications of k-good random matrices are given, establishing links with some well-known combinatorial problems. Finally, the related combinatorial concept of a k-dense set of m-by-n matrices is studied, identifying such sets as blocking sets with respect to (m-k)-dimensional flats in a certain m-by-n matrix geometry and determining their minimum size in special cases.Comment: 25 pages, publishe

Random subcubes as a toy model for constraint satisfaction problems

We present an exactly solvable random-subcube model inspired by the structure of hard constraint satisfaction and optimization problems. Our model reproduces the structure of the solution space of the random k-satisfiability and k-coloring problems, and undergoes the same phase transitions as these problems. The comparison becomes quantitative in the large-k limit. Distance properties, as well the x-satisfiability threshold, are studied. The model is also generalized to define a continuous energy landscape useful for studying several aspects of glassy dynamics.Comment: 21 pages, 4 figure

Multivesicular exocytosis in rat pancreatic beta cells

AIMS/HYPOTHESIS: To establish the occurrence, modulation and functional significance of compound exocytosis in insulin-secreting beta cells. METHODS: Exocytosis was monitored in rat beta cells by electrophysiological, biochemical and optical methods. The functional assays were complemented by three-dimensional reconstruction of confocal imaging, transmission and block face scanning electron microscopy to obtain ultrastructural evidence of compound exocytosis. RESULTS: Compound exocytosis contributed marginally (<5% of events) to exocytosis elicited by glucose/membrane depolarisation alone. However, in beta cells stimulated by a combination of glucose and the muscarinic agonist carbachol, 15-20% of the release events were due to multivesicular exocytosis, but the frequency of exocytosis was not affected. The optical measurements suggest that carbachol should stimulate insulin secretion by ∼40%, similar to the observed enhancement of glucose-induced insulin secretion. The effects of carbachol were mimicked by elevating [Ca(2+)](i) from 0.2 to 2 μmol/l Ca(2+). Two-photon sulforhodamine imaging revealed exocytotic events about fivefold larger than single vesicles and that these structures, once formed, could persist for tens of seconds. Cells exposed to carbachol for 30 s contained long (1-2 μm) serpentine-like membrane structures adjacent to the plasma membrane. Three-dimensional electron microscopy confirmed the existence of fused multigranular aggregates within the beta cell, the frequency of which increased about fourfold in response to stimulation with carbachol. CONCLUSIONS/INTERPRETATION: Although contributing marginally to glucose-induced insulin secretion, compound exocytosis becomes quantitatively significant under conditions associated with global elevation of cytoplasmic calcium. These findings suggest that compound exocytosis is a major contributor to the augmentation of glucose-induced insulin secretion by muscarinic receptor activation

Perinatal outcomes associated with low birth weight in a historical cohort

<p>Abstract</p> <p>Objective</p> <p>To identify perinatal outcomes associated with low birth weight (LBW).</p> <p>Methods</p> <p>A retrospective cohort study in a tertiary maternity hospital. Analysis of the database on 43,499 liveborn infants delivered between 1986 and 2004 with low (n = 6,477) and normal (n = 37,467) birth weight. Outcomes associated with LBW were identified through crude and adjusted risk ratio (RR) and 95%CI with bivariate and multivariate analysis. The main outcomes were: onset of labor, mode of delivery, indication for cesarean section; amniotic fluid, fetal heart rate pattern, Apgar score, somatic gestational age, gender and congenital malformation.</p> <p>Results</p> <p>LBW infants showed more frequently signs of perinatal compromise such as abnormal amniotic fluid volume (especially olygohydramnios), nonreassuring patterns of fetal heart rate, malformation, lower Apgar scores and lower gestational age at birth. They were associated with a greater risk of labor induction and cesarean delivery, but lower risk of forceps.</p> <p>Conclusion</p> <p>There was a clear association between LBW and unfavorable perinatal outcomes.</p

Do Zebra Finch Parents Fail to Recognise Their Own Offspring?

Individual recognition systems require the sender to be individually distinctive and the receiver to be able to perceive differences between individuals and react accordingly. Many studies have demonstrated that acoustic signals of almost any species contain individualized information. However, fewer studies have tested experimentally if those signals are used for individual recognition by potential receivers. While laboratory studies using zebra finches have shown that fledglings recognize their parents by their “distance call”, mutual recognition using the same call type has not been demonstrated yet. In a laboratory study with zebra finches, we first quantified between-individual acoustic variation in distance calls of fledglings. In a second step, we tested recognition of fledgling calls by parents using playback experiments. With a discriminant function analysis, we show that individuals are highly distinctive and most measured parameters show very high potential to encode for individuality. The response pattern of zebra finch parents shows that they do react to calls of fledglings, however they do not distinguish between own and unfamiliar offspring, despite individual distinctiveness. This finding is interesting in light of the observation of a high percentage of misdirected feedings in our communal breeding aviaries. Our results demonstrate the importance of adopting a receiver's perspective and suggest that variation in fledgling contact calls might not be used in individual recognition of offspring