Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis

Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10?1?). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10?3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10?2?, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.     

Melatonin antagonizes colchicine-induced mitotic arrest

Summary Melatonin, in concentrations up to 10^–3 M, showed no effect on mitosis in cultures of HeLa or KB cells. However, when melatonin at 10^–4 M was preincubated with HeLa cells prior to addition of 10^–7 M colchicine, a reduction in the mitotic index, in comparison to colchicine alone, was observed.This work was supported by PHS Grant No. CA 16425.     

Attention modulates synchronized neuronal firing in primate somatosensory cortex

A potentially powerful information processing strategy in the brain is to take advantage of the temporal structure of neuronal spike trains. An increase in synchrony within the neural representation of an object or location increases the efficacy of that neural representation at the next synaptic stage in the brain; thus, increasing synchrony is a candidate for the neural correlate of attentional selection. We investigated the synchronous firing of pairs of neurons in the secondary somatosensory cortex (SII) of three monkeys trained to switch attention between a visual task and a tactile discrimination task. We found that most neuron pairs in SII cortex fired synchronously and, furthermore, that the degree of synchrony was affected by the monkey's attentional state. In the monkey performing the most difficult task, 35% of neuron pairs that fired synchronously changed their degree of synchrony when the monkey switched attention between the tactile and visual tasks. Synchrony increased in 80% and decreased in 20% of neuron pairs affected by attention.     

Erythrocyte cation concentrations and changes in dietary electrolyte intake

Résumé Les taux de Na, K et Mg dans les érythrocytes de 4 hommes sont restés constants lorsque les sujects prenaient des diètes avec des quantités très différentes de cas cathions. Ce résultat indique que dans l'érythrocyte les concentrations de ces ions ne sont pas modifiées par des variations très marquées de la quantité des électrolytes ingestés.

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This work was supported in part by Part I Research Funds from the Veterans Administration. We thank Mrs.S. Hemphill, R. D., for her assistance in the preparation of the experimental diets. The technical assistance of Mrs.J. Verna is gratefully appreciated.     

Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide

The clinical manifestations of AIDS (acquired immune deficiency syndrome) often include neuropsychiatric and neurological deficits, including early memory loss and progressive dementia. HIV (human immunodeficiency virus), the aetiological agent of AIDS, is probably carried by infected macrophages in the central nervous system. The virus enters cells by binding its envelope glycoprotein gp120 to the CD4 antigen present on brain and immune cells. From the data reported in this paper, we now suggest that the neuronal deficits associated with HIV may not be entirely a result of infectivity, but that gp120 shed from HIV could directly produce the neuropathology as a result of its interference with endogenous neurotrophic substances. It is known that an analogue of a sequence contained in vasoactive intestinal peptide (VIP) occurs in all known sequenced gp120 isolates and that VIP is important for neuronal survival in cell culture. Here we show that purified gp120 from two diverse HIV isolates and a recombinant gp120 from a third isolate were all potent in specifically producing significant neuronal cell death in dissociated hippocampal cultures derived from fetal mice, and that this could be reduced by monoclonal antibodies against the murine CD4 antigen and completely antagonized by VIP.     

An exceptional Devonian fish from Australia sheds light on tetrapod origins

The transition from fishes to tetrapods was one of the most dramatic events in the evolution of vertebrates, but many pivotal fossils are incomplete, resulting in gaps in the data that are used for phylogenetic reconstruction. Here we present new observations from the most complete, acid-prepared Devonian tetrapodomorph fish yet discovered, Gogonasus, which was previously placed just crownward of Kenichthys and rhizodontids, the most primitive taxa on the tetrapod lineage. Unexpectedly, Gogonasus shows a mosaic of plesiomorphic and derived tetrapod-like features. Whereas the braincase and dermal cranial skeleton exhibit generalized morphologies with respect to Eusthenopteron or Panderichthys, taxa that are traditionally considered to be phyletically close to tetrapods, the presence of a deeply invaginated, wide spiracle, advanced internal spiracular architecture and near-horizontal hyomandibula are specialized features that are absent from Eusthenopteron. Furthermore, the pectoral fin skeleton of Gogonasus shares several features with that of Tiktaalik, the most tetrapod-like fish. A new phylogenetic analysis places Gogonasus crownward of Eusthenopteron as the sister taxon to the Elpistostegalia. Aspects of the basic tetrapod limb skeleton and middle ear architecture can now be traced further back within the tetrapodomorph radiation.     

Why There's Nothing Wrong With Systems Thinking a Little Chaos Won't Fix? A Critique of Modern Systems Theory and the Practice of Organizational Change It Informs

We find ourselves at the dawning of a new millennium, uneasy denizens of a world of growing flux. The models of reality on which we rely in our continuing effort to master the turbulent and hypercompetitive marketplace are failing us. Even the much touted 20th-century innovation referred to by Peter Senge in his 1990 bestseller of the same name as the fifth discipline, that is, systems thinking, turns out to be less than adequate to the task. Therein lies the central purpose of this paper: to demonstrate why there's nothing wrong with systems thinking that a little chaos can't remedy. My intent is twofold: first, to expose the problematic partialness of this paradigm, given its tendency to direct one's focus to not to the whole system, but to its exterior half, and, second, to introduce the reader to Chaos, the powerful cosmology now emerging from 20th-century science, as a science of whole wholes—one that enables the practitioner of management and systems sciences to comprehend the system's externality, its subtle within, and most importantly, the crucial relationship between them.