University College London

About: University College London is a education organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 81105 authors who have published 210603 publications receiving 9868552 citations. The organization is also known as: UCL & University College, London.

Primordial germ cells in the mouse embryo during gastrulation.

Abstract: With the aid of a whole-mount technique, we have detected a small cluster of alkaline phosphatase (ALP)-positive cells in whole mounts of mid-primitive-streak-stage embryos, 7-7 1/4 days post coitum (dpc). Within the cluster, about 8 cells contain a small cytoplasmic spot, intensely stained for ALP activity and possibly associated with an active Golgi complex. The cluster lies just posterior to the definitive primitive streak in the extraembryonic mesoderm, separated from the embryo by the amniotic fold. Towards the end of gastrulation, the number of cells containing the ALP-positive spot rises to between 50 and 80. Thereafter the number of cells in the extraembryonic cluster declines, and similar cells start to be seen in the mesoderm of the primitive streak and then in the endoderm. At 8 dpc, about 125 ALP-stained cells are found, mainly in the hindgut endoderm and also at the base of the allantois, their appearance and location at this stage agreeing closely with previous reports on primordial germ cells (PGCs). Embryos from which the cluster area has been removed at the 7-day stage are devoid of PGCs after culture for 48 h, whereas the excised tissue is rich in PGCs. We argue that the cells in the cluster are indeed primordial germ cells, at a stage significantly earlier than any reported previously. This would indicate that the PGC lineage in the mouse is set aside at least as early as 7 dpc, possibly as one of the first 'mesodermal' cell types to emerge, and that its differentiation, as expressed by ALP activity, is gradual.

Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases

Abstract: The complement and immunoglobulin receptors are the major phagocytic receptors involved during infection. However, only immunoglobulin-dependent uptake results in a respiratory burst and an inflammatory response in macrophages. Rho guanosine triphosphatases (molecular switches that control the organization of the actin cytoskeleton) were found to be essential for both types of phagocytosis. Two distinct mechanisms of phagocytosis were identified: Type I, used by the immunoglobulin receptor, is mediated by Cdc42 and Rac, and type II, used by the complement receptor, is mediated by Rho. These results suggest a molecular basis for the different biological consequences that are associated with phagocytosis.

The estimation and significance of the logarithm of a ratio of frequencies.

Abstract: It is occasionally useful to estimate the logarithm of the ratio of two classes in a sample. But a much more important case is discussed by Woolf (1955). Out of n cases of a disease, h had the character a and k the character p. Out of N unaffected persons, H had the character a and hthe character /3. For example, of 1490 cases of peptic ulcer in London investigated by Aird, Bentall, Mehigan & Roberts (1954), h=Y11, k=579, while among 8797 controls, H =4578, K = 4219, where the characters a and are membership of blood groups 0 and A . Hence Woolf calculated hK/kH = 1.4500, In (hK/kH) = 0.3716, where In x= logp. Suppose that the frequencies of groups 0 and A in all cases of peptic ulcer in London were p andq, among allother Londoners P and Q, then ln ( h K / k H ) is an efficient estimate of In (pQ/qP) . But it has a bias which is not always negligible. The estimate hK/kH has formally an infinite expectation, and all the moments of its distribution are infinite. For there is a finite, though very small, probability that either k or H should be zero. Even if such cases are neglected it has a bias of order n-1. As pointed out by Haldane & Maynard Smith (1056), t.he bias of h K / { ( k + 1) ( H + 1)) tends to zero more rapidly than any negative power of n or X . Similarly, all the moments of the distribution of the logarithm are formally infinite, since any of h, k , H and K may be zero with a finite probability. This fact by itself is unimportant, but i t is an indication that a less biased expression can be found. Since the two samples were taken independently, their sampling errors are uncorrelated, and we can therefore consider the estimation of In ( p l y ) . Let h = p n +a, k =qn -01. I am assuming sampling from an infinite population, and shall neglect the errors due to the fact that this is not so. Then

Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage.

Abstract: The developmental origin of oligodendrocyte progenitors (OLPs) in the forebrain has been controversial. We now show, by Cre-lox fate mapping in transgenic mice, that the first OLPs originate in the medial ganglionic eminence (MGE) and anterior entopeduncular area (AEP) in the ventral forebrain. From there, they populate the entire embryonic telencephalon including the cerebral cortex before being joined by a second wave of OLPs from the lateral and/or caudal ganglionic eminences (LGE and CGE). Finally, a third wave arises within the postnatal cortex. When any one population is destroyed at source by the targeted expression of diphtheria toxin, the remaining cells take over and the mice survive and behave normally, with a normal complement of oligodendrocytes and myelin. Thus, functionally redundant populations of OLPs compete for space in the developing brain. Notably, the embryonic MGE- and AEP-derived population is eliminated during postnatal life, raising questions about the nature and purpose of the competition.

Tonic dopamine: opportunity costs and the control of response vigor.

Abstract: Rationale Dopamine neurotransmission has long been known to exert a powerful influence over the vigor, strength, or rate of responding. However, there exists no clear understanding of the computational foundation for this effect; predominant accounts of dopamine’s computational function focus on a role for phasic dopamine in controlling the discrete selection between different actions and have nothing to say about response vigor or indeed the freeoperant tasks in which it is typically measured. Objectives We seek to accommodate free-operant behavioral tasks within the realm of models of optimal control and thereby capture how dopaminergic and motivational manipulations affect response vigor. Methods We construct an average reward reinforcement learning model in which subjects choose both which action to perform and also the latency with which to perform it. Optimal control balances the costs of acting quickly against the benefits of getting reward earlier and thereby chooses a best response latency. Results In this framework, the long-run average rate of reward plays a key role as an opportunity cost and mediates motivational influences on rates and vigor of responding. We review evidence suggesting that the average reward rate is reported by tonic levels of dopamine putatively in the nucleus accumbens. Conclusions Our extension of reinforcement learning models to free-operant tasks unites psychologically and computationally inspired ideas about the role of tonic dopamine in striatum, explaining from a normative point of view why higher levels of dopamine might be associated with more vigorous responding.