On the nature of visible chromosomal gaps and breaks

From the earliest days of chromosomal aberration studies, the distinction, nature and origin of light-microscope observed "gaps" and "breaks" have been topics for debate and controversy. In this paper we survey, briefly, the various ideas that have appeared in the very extensive literature, and attempt to evaluate them in the light of our current understanding of chromosome structure and aberration formation. Attention is drawn to the problems of interpretation caused by G2/S cell imprecision.     

Locality and gaps in RNA comparison.

Locality is an important and well-studied notion in comparative analysis of biological sequences. Similarly, taking into account affine gap penalties when calculating biological sequence alignments is a well-accepted technique for obtaining better alignments. When dealing with RNA, one has to take into consideration not only sequential features, but also structural features of the inspected molecule. This makes the computation more challenging, and usually prohibits the comparison only to small RNAs. In this paper we introduce two local metrics for comparing RNAs that extend the Smith-Waterman metric and its normalized version used for string comparison. We also present a global RNA alignment algorithm which handles affine gap penalties. Our global algorithm runs in O(m(2)n(1 + lg n/m)) time, while our local algorithms run in O(m(2)n(1 + lg n/m)) and O(n(2)m) time, respectively, where m 相似文献   

Calcium waves in astrocytes-filling in the gaps.

Stimulus-evoked cellular responses are sometimes organized in the form of propagating waves of cytoplasmic Ca2+ increase. Ca2+ waves can be elicited in cultured astrocytes by the neurotransmitter glutamate; however, the propagation mechanism is unknown. Here, qualitative and quantitative features of propagation suggest that astrocytic Ca2+ waves are mediated by an intracellular signal that crosses intercellular junctions. The role of gap junctions in cell-cell Ca2+ wave propagation was specifically tested. Functional gap junctions were demonstrated using a noninvasive fluorescence recovery method and the gap junction blockers halothane and octanol. Gap junction closure prevented intracellular waves from propagating between cells without affecting the velocity of the intracellular wave itself. The pivotal role played by the gap junction creates the potential for dynamic changes in glial connectivity and long-range glial signaling.     

Blocking and paradigm gaps

Gaps in morphological paradigms are often explained in terms of blocking: generating one form is blocked by the existence of a paraphrase. Another way of thinking about paradigm gaps dissociates their existence from competition between forms. Unlike in competition-based approaches, systematic gaps can be seen as true gaps; the system might not generate a certain form, but this form is not considered in comparison to others. Adopting this latter approach, we argue that inflectional paradigms are neither morphosyntactic primitives nor the result of competition. This claim is supported by data from two unrelated languages. For Hebrew, we demonstrate that a passive gap is not the result of competition with analytic paraphrases. For Latin, we show that a cyclic, syntax-based approach is superior to a theory that generates nonactive verbs in the lexicon and has them compete against each other. Systematic paradigm gaps are thus argued to result from syntactic structure building, without competition regulating independent morphological constructions.     

Rapid significance estimation in local sequence alignment with gaps.

In order to assess the significance of sequence alignments, it is crucial to know the distribution of alignment scores of pairs of random sequences. For gapped local alignment, it is empirically known that the shape of this distribution is of the Gumbel form. However, the determination of the parameters of this distribution is a computationally very expensive task. We present a new algorithmic approach which allows estimation of the more important of the Gumbel parameters at least five times faster than the traditional methods. Actual runtimes of our algorithm between less than a second and a few minutes on a workstation bring significance estimation into the realm of interactive applications.     

A practical approach to significance assessment in alignment with gaps.

Current numerical methods for assessing the statistical significance of local alignments with gaps are time consuming. Analytical solutions thus far have been limited to specific cases. Here, we present a new line of attack to the problem of statistical significance assessment.We combine this new approach with known properties of the dynamics of the global alignment algorithm and high performance numerical techniques and present a novel method for assessing significance of gaps within practical time scales. The results and performance of these new methods test very well against tried methods with drastically less effort.     

Acute intraoperative arterial lengthening for closure of large vascular gaps.

This study demonstrates the feasibility of acute extraluminal expansion to elongate arteries intraoperatively in order to overcome defects too large to be repaired primarily. Twenty Sprague-Dawley rats were divided into two groups: an expander-elongation group and a nonexpanded control group of 10 rats each. Arterial resections were performed ranging from 6 to 22 mm. A miniaturized tissue expander was used to stretch vessels in three consecutive cycles over a 15- to 20-minute period (expander-elongation group). Defects twice as long as those which could be overcome by mobilization alone (nonexpanded control group) could be closed following the application of this technique without thrombosis. Initial laboratory findings and the application of this method in a clinical case are presented.     

Cell migration through small gaps

Cell motility is a fundamental process associated with many phenomena in nature, such as immune response, wound healing, and cancer metastasis. In these processes, cells must squeeze through cell layers, and we characterize this ability to actively produce forces and simultaneously adapt their shapes. We have measured forward forces up to 15 nN that a migrating keratocyte was able to generate, in order to adjust its shape and successfully force its way under and past an obstacle. We also observed that 34 nN was capable of stalling the cell’s forward motion. Furthermore, we measured that under compression stresses up to 1,165 pN/μm² (1,165 Pa), cell morphology, and velocity remained unchanged. Additionally, we found that keratocytes were able to compress themselves up to 80% vertically in order to squeeze through a gap as small as 500 nm.Authors Claudia A. Brunner, Allen Ehrlicher, and Michael Goegler have contributed equally to this work.     

Bridging gaps in phospholipid transport

Phospholipid transport between membranes is a fundamental aspect of organelle biogenesis in eukaryotes; however, little is know about this process. A significant body of data demonstrates that newly synthesized phospholipids can move between membranes by routes that are independent of the vesicular traffic that carries membrane proteins. Evidence continues to accumulate in support of a system for phospholipid transport that occurs at zones of apposition and contact between donor membranes - the source of specific phospholipids - and acceptor membranes that are unable to synthesize the necessary lipids. Recent findings identify some of the lipids and proteins that must be present on membranes for inter-organelle phospholipid transport to occur between the endoplasmic reticulum and mitochondria or Golgi. These data suggest that protein and lipid assemblies on donors and acceptors promote membrane docking and facilitate lipid movement.     

Scaling laws and similarity detection in sequence alignment with gaps.

We study the problem of similarity detection by sequence alignment with gaps, using a recently established theoretical framework based on the morphology of alignment paths. Alignments of sequences without mutual correlations are found to have scale-invariant statistics. This is the basis for a scaling theory of alignments of correlated sequences. Using a simple Markov model of evolution, we generate sequences with well-defined mutual correlations and quantify the fidelity of an alignment in an unambiguous way. The scaling theory predicts the dependence of the fidelity on the alignment parameters and on the statistical evolution parameters characterizing the sequence correlations. Specific criteria for the optimal choice of alignment parameters emerge from this theory. The results are verified by extensive numerical simulations.