Primary neurons that express the L2/HNK-1 carbohydrate during early development in the zebrafish

In zebrafish, many nerve pathways in both the CNS and periphery are pioneered by a small and relatively simple set of ‘primary’ neurons that arise in the early embryo. We now have used monoclonal antibodies to show that, as they develop, primary neurons of several functional classes express on their surfaces the L2/HNK-1 tetrasaccharide that is associated with a variety of cell surface adhesion molecules. We have studied the early labeling patterns of these neurons, as well as some non-neural cells, and found that the time of onset and intensity of immunolabeling vary specifically according to cell type. The first neuronal expression is by Rohon-Beard and trigeminal ganglion neurons, both of which are primary sensory neurons that mediate touch sensitivity. These cells express the epitope very strongly on their growth cones and axons, permitting study of their development unobscured by labeling in other cells. Both types initiate axogenesis at the same early time, and appear to be the first neurons in the embryo to do so. Their peripheral neurites display similar branching patterns and have similar distinctive growth cone morphologies. Their central axons grow at the same rate along the same longitudinal fiber pathway, but in opposite directions, and where they meet they appear to fasciculate with one another. The similarities suggest that Rohon-Beard and trigeminal ganglion neurons, despite their different positions, share a common program of early development. Immunolabeling is also specifically present on a region of the brain surface where the newly arriving trigeminal sensory axons will enter the brain. Further, the trigeminal expression of the antigen persists in growth cones during the time that they contact an individually identified central target neuron, the Mauthner cell, which also expresses the epitope. These findings provide descriptive evidence for possible roles of L2/HNK-1 immunoreactive molecules in axonal growth and synaptogenesis

Imaging the cool gas, dust, star formation, and AGN in the first galaxies

When, and how, did the first galaxies and supermassive black holes (SMBH) form, and how did they reionization the Universe? First galaxy formation and cosmic reionization are among the last frontiers in studies of cosmic structure formation. We delineate the detailed astrophysical probes of early galaxy and SMBH formation afforded by observations at centimeter through submillimeter wavelengths. These observations include studies of the molecular gas (= the fuel for star formation in galaxies), atomic fine structure lines (= the dominant ISM gas coolant), thermal dust continuum emission (= an ideal star formation rate estimator), and radio continuum emission from star formation and relativistic jets. High resolution spectroscopic imaging can be used to study galaxy dynamics and star formation on sub-kpc scales. These cm and mm observations are the necessary compliment to near-IR observations, which probe the stars and ionized gas, and X-ray observations, which reveal the AGN. Together, a suite of revolutionary observatories planned for the next decade from centimeter to X-ray wavelengths will provide the requisite panchromatic view of the complex processes involved in the formation of the first generation of galaxies and SMBHs, and cosmic reionization.Comment: 8 pages total. White paper submitted to the Astro 2010 Decadal Surve

THE RESISTANCE TO FIBRINOLYTIC ACTIVITY OF THE HEMO- LYTIC STREPTOCOCCUS WITH SPECIAL REFERENCE TO PATIENTS WITH RHEUMATIC FEVER AND RHEUMATOID (ATROPHIC) ARTHRITIS'

Recently Tillett and Garner (1) have demonstrated that broth cultures of hemolytic streptococci of human origin rapidly liquefy the fibrinclot of human plasma. Cultures of other species of bacteria obtained from human beings fail to exhibit this property. Tillett, Edwards and Garner (2) further found that the plasma clot from patients convalescent from acute hemolytic streptococcal infections was highly resistant to the action of broth cultures of a human hemolytic streptococcus. The observations of Tillett and his coworkers were confirmed by Hadfield, Magee and Perry (3). Previously, we (4, 5, 6) have studied groups of patients with rheumatic fever and rheumatoid arthritis to determine what, if any, relationship exists between streptococcal infection and these diseases. In continuing these studies, we have determined the resistance to fibrinolysis of the blood plasma of patients with rheumatic fever and rheumatoid arthritis and of control groups of patients. METHODS OF STUDY All patients were studied while in the hospital. The methods employed in the determination of the resistance to fibrinolysis of blood plasma followed closely the method described by Tillett and his coworkers (1, 2). At weekly intervals 5 cc. of blood were collected. Potassium oxalate, 0.01 gram per 5 cc. of blood, was employed as an anticoagulant. The plasma was separated by centrifugalization and was used within two hours after its withdrawal. A hour cultures of this organism were grown in veal muscle infusion broth, adjusted to a pH of 7.2 and containing one per cent of peptone and 0.2 per cent of Na2HPO4. To 0.2 cc. of fresh oxalated plasma was added 0.8 cc. of sterile physiological salt solution. To this 0.5 cc. of a fresh broth culture of the CO strain of the hemolytic streptococcus was added and well mixed. Then 0.25 cc. of a 0.25 per cent sterile solution of CaCl2 was added and well mixed. The tubes were placed immediately in a water bath at 37.5°C. With repeated observations the times of solid coagulation and, finally, complete dissolution of the clot were recorded. All tests in which the plasma clot was resistant to dissolution after 24 hours' incubation were arbitrarily terminated. The classification of the degree of resistance of the plasma clot as suggested by Tillett, Edwards and Garner (2) was followed. The highest degree of resistance shown by a patient's plasma during the period of observation was utilized in the classification shown in RESULTS Determinations of the resistance to fibrinolysis of 520 samples of plasma from 135 individuals were made. Their ages varied between thirteen and seventy years. No correlation could be established between the age of the individual and the ability to develop resistance to fibrinolysis. The plasmas from groups of individuals without evidence of hemolytic streptococcal infection were studied. Samples of plasma from fourteen apparently normal laboratory workers were followed at frequent intervals for several months. A group of twenty-two patients with pulmonary tuberculosis, lobar pneumonia, herpes zoster and lung abscess were studied on fifty-one occasions. 11

Risk for Avian Influenza Virus Exposure at Human–Wildlife Interface

To assess risk for human exposure to avian influenza viruses (AIV), we sampled California wild birds and marine mammals during October 2005–August 2007and estimated human–wildlife contact. Waterfowl hunters were 8 times more likely to have contact with AIV-infected wildlife than were persons with casual or occupational exposures (p<0.0001)

Francesco Ruggiero 1957-2007

Francesco Ruggiero (1957–2007)was a brilliant accelerator physicist, an inventive researcher, a great collaborator, an excellent mentor, and a true gentleman. We here take a look at Francesco’s scientific work, and highlight some of his contributions to accelerator physics. More details can be found in the slides presented by the speakers of the Francesco Ruggiero Memorial Symposium held at CERN on 3 October 200

Randall-Sundrum black holes and strange stars

It has recently been suggested that the existence of bare strange stars is incompatible with low scale gravity scenarios. It has been claimed that in such models, high energy neutrinos incident on the surface of a bare strange star would lead to catastrophic black hole growth. We point out that for the flat large extra dimensional case, the parts of parameter space which give rise to such growth are ruled out by other methods. We then go on to show in detail how black holes evolve in the the Randall-Sundrum two brane scenario where the extra dimensions are curved. We find that catastrophic black hole growth does not occur in this situation either. We also present some general expressions for the growth of five dimensional black holes in dense media.Comment: 16 pages, more numerics has lead to different path to same conclusion. Accepted in PR

The Mre11-Rad50-Nbs1 complex mediates activation of TopBP1 by ATM

The activation of ATR-ATRIP in response to double-stranded DNA breaks (DSBs) depends upon ATM in human cells and Xenopus egg extracts. One important aspect of this dependency involves regulation of TopBP1 by ATM. In Xenopus egg extracts, ATM associates with TopBP1 and thereupon phosphorylates it on S1131. This phosphorylation enhances the capacity of TopBP1 to activate the ATR-ATRIP complex. We show that TopBP1 also interacts with the Mre11-Rad50-Nbs1 (MRN) complex in egg extracts in a checkpoint-regulated manner. This interaction involves the Nbs1 subunit of the complex. ATM can no longer interact with TopBP1 in Nbs1-depleted egg extracts, which suggests that the MRN complex helps to bridge ATM and TopBP1 together. The association between TopBP1 and Nbs1 involves the first pair of BRCT repeats in TopBP1. In addition, the two tandem BRCT repeats of Nbs1 are required for this binding. Functional studies with mutated forms of TopBP1 and Nbs1 suggested that the BRCT-dependent association of these proteins is critical for a normal checkpoint response to DSBs. These findings suggest that the MRN complex is a crucial mediator in the process whereby ATM promotes the TopBP1-dependent activation of ATR-ATRIP in response to DSBs

‘The object is to change the heart and soul’: Financial incentives, planning and opposition to new housebuilding in England

© The Author(s) 2020. In 2014 the UK government announced plans to reduce opposition to housing development by making a direct payment to households in England. 1 This was part of a wider experiment with behavioural economics and financial inducements in planning policy. In this paper, we explore this proposal, named ‘Development Benefits’, arguing it offers important insights into how the governing rationality of neoliberalism attempts to govern both planning and opposition to development by replacing political debate with a depoliticised economic rationality. Drawing on householder and key player responses to the Development Benefits proposal we highlight significant levels of principled objection to the replacement of traditional forms of planning reason with financial logics. The paper therefore contributes to understandings of planning as a site of ongoing resistance to neoliberal rationalities. We conclude by questioning whether Development Benefits represent a particular strand of ‘late neoliberal’ governmentality, exploring the potential for an alternative planning rationality to contest the narrow marketisation of planning ideas and practices