The Use of Biomarker Expression to Characterize Neoplastic Processes

Biomarkers have been used by pathologists to aid the diagnosis of tumors for almost three decades. Their use has resulted in the re-evaluation and reclassification of several types of tumors. Currently, biomarkers are required to differentiate certain specific tumors with similar histologic patterns. Additional uses of biomarkers in the characterization of neoplastic processes are discussed including their use in prognosis, detecting early neoplastic processes, identifying tumor recurrence, measuring the effectiveness of various therapies (surrogate end point biomarkers), and identifying targets for novel therapies including immunotherapy and gene therapy. We propose that these newer uses of biomarkers will be just as important to pathology in the future as the uses of biomarkers in diagnosis have been over the past two decades.     

D1-Like Dopamine Receptor-Mediated Function in Congenic Mutants with D1 vs. D5 Receptor “Knockout”

Current understanding of the functional roles of individual dopamine D₁-like [D₁, D₅] and D₂-like [D_2L/S, D₃, D₄] receptor subtypes remains incomplete. In particular, the lack of pharmacological agonists and antagonists able to distinguish between D₁ and D₅ receptors means that any differential roles in the regulation of behavior are poorly understood. Mutant mice with targeted gene deletion (“knockout”) of individual dopamine receptor subtypes offer an important alternative approach to resolving these functional roles. In congenic D₁ mutants examined ethologically, progressive increases in specific topographies of behavior over wildtypes were considerably greater than those in D₁ mutants on a mixed genetic background; D₁ knockout appears to influence the neuronal substrate(s) of habituation to disrupt sculpture of the changing topography of behavior from initial exploration through to quiescence. Similarly, the D₁ receptor appears to regulate specific topographies of orofacial movement in the mouse as these are “sculpted” in a time-dependent manner. Although the well-recognized role of the D₁-like family in regulating several aspects of behavioral topography has been assumed to involve primarily D₁ receptors, this presumption may require modification to accommodate a subtle but not negligible role for their D₅ counterparts as evidenced in the phenotype of congenic D₅ mutants.     

Modifications of Neuronal Activity in the Medial Vestibular Nucleus during Long-Term Vibration

The impulse background activity (BA) of neurons of the rat medial vestibular nucleus (MVN) was subjected to computer analysis, and its modifications related to long-term vibration were studied. It was shown that following 5 days of 2-h-long vibration sessions, statistically significant changes in some basic characteristics of BA generated by MVN neurons were observed. More than a twofold increase in the mean BA frequency and substantial shifts practically of all statistical BA parameters were found after 10 days of vibration. Following a 15-day-long vibration, MVN neurons showed a clear-cut tendency to restore control values of the BA indices, which probably was related to adaptation processes.     

情绪记忆权衡与拓宽效应及其认知神经机制

情绪图片能比中性图片产生更好的记忆效果。然而近年研究发现，对于复杂场景图片，情绪诱发的记忆增强并非单一的过程，而包含两个相反的现象：情绪信息既可能选择性地增强场景中具有情感色彩的中心记忆，并带来背景记忆的下降，诱发情绪记忆权衡效应；也可能同时增强中心和背景记忆，诱发情绪记忆拓宽效应。两种现象的发生取决于记忆信息特性（情绪效价、中心-背景联结程度）及记忆过程（编码、巩固和提取）相关的诸多因素，而其背后的机制仍未明晰。当前该领域存在情绪记忆权衡是否是一种不由注意所介导的自动化过程的争论，另有少数研究考察了与记忆权衡效应相关的脑网络，而针对记忆拓宽效应机制的研究仍较为匮乏。未来需从行为和神经层面，对比情绪诱发的记忆权衡与拓宽效应的发生机制，针对二者的自动化特性、涉及的记忆表征形式等问题深入研究，并将这些效应拓展至空间之外的维度，以系统揭示情绪信息选择性增强记忆现象背后的深层原因。     

Disruptive camouflage impairs object recognition

Whether hiding from predators, or avoiding battlefield casualties, camouflage is widely employed to prevent detection. Disruptive coloration is a seemingly well-known camouflage mechanism proposed to function by breaking up an object''s salient features (for example their characteristic outline), rendering objects more difficult to recognize. However, while a wide range of animals are thought to evade detection using disruptive patterns, there is no direct experimental evidence that disruptive coloration impairs recognition. Using humans searching for computer-generated moth targets, we demonstrate that the number of edge-intersecting patches on a target reduces the likelihood of it being detected, even at the expense of reduced background matching. Crucially, eye-tracking data show that targets with more edge-intersecting patches were looked at for longer periods prior to attack, and passed-over more frequently during search tasks. We therefore show directly that edge patches enhance survivorship by impairing recognition, confirming that disruptive coloration is a distinct camouflage strategy, not simply an artefact of background matching.     

The feeding behaviour of New Zealand Dolomedes species (Araneae: Pisauridae)

Abstract

The prey spectrum and predatory behaviour of Dolomedes sp. (‘D. III’), D. aquaticus, and D. minor are described from a series of field and laboratory investigations, the former made around Nelson and on Banks Peninsula, Canterbury, during summer months. All species are large, robust spiders that capture prey by directly seizing it in their mouthparts, not using silk at any stage of predation. Adult aquatic insects are their main prey, but these are available only irregularly during their activity period (night-time), and the spiders are opportunistic in their feeding habits. They will eat virtually any available small animal, and at least the largest species, D. III, is able to capture and ingest small fishes. Dead as well as live organisms are taken. Furthermore, the spiders are capable of feeding infrequently; when feeding on small prey organisms they may capture several sequentially, to increase the size of the meal. Live prey is caught while it is in flight, or on the ground, or at the water surface (rarely submerged), and is detected primarily by touch and airborne sound; vision is unnecessary for normal predation. Prey is captured very rapidly, even though this may initially involve a dash of up to 40 cm across the water surface to locate the organism. Stages in the behaviour of an active spider, from waiting for prey to grooming after ingestion, are described.     

Brain wiring with composite instructions

The quest for molecular mechanisms that guide axons or specify synaptic contacts has largely focused on molecules that intuitively relate to the idea of an “instruction.” By contrast, “permissive” factors are traditionally considered background machinery without contribution to the information content of a molecularly executed instruction. In this essay, I recast this dichotomy as a continuum from permissive to instructive actions of single factors that provide relative contributions to a necessarily collaborative effort. Individual molecules or other factors do not constitute absolute instructions by themselves; they provide necessary context for each other, thereby creating a composite that defines the overall instruction. The idea of composite instructions leads to two main conclusions: first, a composite of many seemingly permissive factors can define a specific instruction even in the absence of a single dominant contributor; second, individual factors are not necessarily related intuitively to the overall instruction or phenotypic outcome.     

Proof of the Feldman–Karlin conjecture on the maximum number of equilibria in an evolutionary system

Feldman and Karlin conjectured that the number of isolated fixed points for deterministic models of viability selection and recombination among n possible haplotypes has an upper bound of 2ⁿ−1. Here a proof is provided. The upper bound of 3ⁿ⁻¹ obtained by Lyubich et al. (2001) using Bézout’s Theorem (1779) is reduced here to 2ⁿ through a change of representation that reduces the third-order polynomials to second order. A further reduction to 2ⁿ−1 is obtained using the homogeneous representation of the system, which yields always one solution ‘at infinity’. While the original conjecture was made for systems of selection and recombination, the results here generalize to viability selection with any arbitrary system of bi-parental transmission, which includes recombination and mutation as special cases. An example is constructed of a mutation-selection system that has 2ⁿ−1 fixed points given any n, which shows that 2ⁿ−1 is the sharpest possible upper bound that can be found for the general space of selection and transmission coefficients.     

Animal camouflage: compromise or specialize in a 2 patch-type environment?

Many animals possess camouflage markings that reduce the riskof detection by visually hunting predators. A key aspect ofcamouflage involves mimicking the background against which theanimal is viewed. However, most animals experience a wide varietyof backgrounds and cannot change their external appearance tomatch each selectively. We investigate whether such animalsshould adopt camouflage specialized with respect to one backgroundor adopt a compromise between the attributes of multiple backgrounds.We do this using a model consisting of predators that hunt preyin patches of 2 different types, where prey adopt the camouflagethat minimizes individual risk of predation. We show that theoptimal strategy of the prey is affected by a number of factors,including the relative frequencies of the patch types, the traveltime of predators between patches, the mean prey number in eachpatch type, and the trade-off function between the levels ofcrypsis in the patch types. We find evidence that both specialistand compromise strategies of prey camouflage are favored underdifferent model parameters, indicating that optimal concealmentmay not be as straightforward as previously thought.