Manual chronostasis: tactile perception precedes physical contact

When saccading to a silent clock, observers sometimes think that the second hand has paused momentarily. This effect has been termed chronostasis and occurs because observers overestimate the time that they have seen the object of an eye movement. They seem to extrapolate its appearance back to just prior to the onset of the saccade rather than the time that it is actually fixated on the retina. Here, we describe a similar effect following an arm movement: subjects overestimate the time that their hand has been in contact with a newly touched object. The illusion's magnitude suggests backward extrapolation of tactile perception to a moment during the preceding reach. The illusion does not occur if the arm movement triggers a change in a continuously visible visual target: the time of onset of the change is estimated correctly. We hypothesize that chronostasis-like effects occur when movement produces uncertainty about the onset of a sensory event. Under these circumstances, the time at which neurons with receptive fields that shift in the temporal vicinity of a movement change their mappings may be used as a time marker for the onset of perceptual properties that are only established later.     

Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death

The cytokine interleukin-1 (IL-1) has two main pro-inflammatory forms, IL-1α and IL-1β, which are central to host responses to infection and to damaging sterile inflammation. Processing of IL-1 precursor proteins to active cytokines commonly occurs through activation of proteases, notably caspases and calpains. These proteases are instrumental in cell death, and inflammation and cell death are closely associated, hence we sought to determine the impact of cell death pathways on IL-1 processing and release. We discovered that apoptotic regulation of caspase-8 specifically induced the processing and release of IL-1β. Conversely, necroptosis caused the processing and release of IL-1α, and this was independent of IL-1β processing and release. These data suggest that the mechanism through which an IL-1-expressing cell dies dictates the nature of the inflammatory mechanism that follows. These insights may allow modification of inflammation through the selective targeting of cell death mechanisms during disease.     

Small Molecule-facilitated Degradation of ANO1 Protein: A NEW TARGETING APPROACH FOR ANTICANCER THERAPEUTICS

ANO1, a calcium-activated chloride channel, is highly expressed and amplified in human cancers and is a critical survival factor in these cancers. The ANO1 inhibitor CaCC_inh-A01 decreases proliferation of ANO1-amplified cell lines; however, the mechanism of action remains elusive. We explored the mechanism behind the inhibitory effect of CaCC_inh-A01 on cell proliferation using a combined experimental and in silico approach. We show that inhibition of ANO1 function is not sufficient to diminish proliferation of ANO1-dependent cancer cells. We report that CaCC_inh-A01 reduces ANO1 protein levels by facilitating endoplasmic reticulum-associated, proteasomal turnover of ANO1. Washout of CaCC_inh-A01 rescued ANO1 protein levels and resumed cell proliferation. Proliferation of newly derived CaCC_inh-A01-resistant cell pools was not affected by CaCC_inh-A01 as compared with the parental cells. Consistently, CaCC_inh-A01 failed to reduce ANO1 protein levels in these cells, whereas ANO1 currents were still inhibited by CaCC_inh-A01, indicating that CaCC_inh-A01 inhibits cell proliferation by reducing ANO1 protein levels. Furthermore, we employed in silico methods to elucidate novel biological functions of ANO1 inhibitors. Specifically, we derived a pharmacophore model to describe inhibitors capable of promoting ANO1 degradation and report new inhibitors of ANO1-dependent cell proliferation. In summary, our data demonstrate that inhibition of the channel activity of ANO1 is not sufficient to inhibit ANO1-dependent cell proliferation, indicating that the role of ANO1 in cancer only partially depends on its function as a channel. Our results provide an impetus for gaining a deeper understanding of ANO1 modulation in cells and introduce a new targeting approach for antitumor therapy in ANO1-amplified cancers.     

Catecholamine and thyroid hormone influence on brown fat Na+, K+-ATPase activity and thermogenesis in the rat

Resting oxygen consumption (VO2) before and after injection of noradrenaline (NA), and plasma triiodothyronine levels were elevated in hyperthyroid and hyperphagic cafeteria fed rats, but were reduced in 4d-fasted and hypothyroid animals compared to controls. Refeeding fasted rats with a single carbohydrate meal caused all of these parameters to increase towards control levels. In vivo turnover, and in vitro release of NA brown adipose tissue (BAT) was elevated in cafeteria fed rats but remained unaltered in other groups and levels and uptake of NA in BAT were similar for all rats. Basal and NA stimulated Na+,K+-ATPase activity in BAT was increased in cafeteria and hyperthyroid rats and reduced in fasted and hypothyroid animals compared to control and refed groups. A highly significant correlation (r = 0.977), (P less than 0.001), found between the in vitro activity of this enzyme and resting VO2 in all rats, indicates that BAT Na+,K+-ATPase may be involved in the thermogenic responses to diet, catecholamines and thyroid hormones.     

Comparison of the DNA sequence of the Crawford small-plaque variant of polyomavirus with those of polyomaviruses A2 and strain 3.

The DNA sequence of two wild-type strains of polyomavirus (A2 and strain 3) are known. We have determined the majority of the DNA sequence of a third strain, the Crawford small-plaque virus. This virus has been noted for its capacity to induce readily detected tumor-specific transplantation antigen in hamster cells, a property that is most likely attributable to an altered middle T-antigen. A comparison of its DNA sequence with those of the A2 and strain 3 viruses reveals numerous nucleotide substitutions, insertions, and deletions throughout the genome. Most sequence changes in coding regions are silent mutations; however, variability in proteins can be predicted from these sequence data at 5 locations in middle T-antigen, 10 in large T-antigen, and 10 in VP1. The Crawford small-plaque virus noncoding regulatory region contains, in addition to nucleotide substitutions, a 44-base-pair tandem repeat of sequences on the late side of the origin of DNA replication.     

VEGETATIVE AND FERTILE STRUCTURES OF CYATHOTHECA VENTILARIA FROM THE UPPER PENNSYLVANIAN OF THE APPALACHIAN BASIN

Permineralized stems, leaves and a fertile structure assignable to Cyathotheca Taylor are described from the Late Pennsylvanian Duquesne Coal of eastern Ohio. The new material, C. ventilaria sp. nov., provides the first evidence of vegetative structures for the genus. Vegetative parts are referred to the fertile fragments based upon distinctive vascular morphology, common histological features, and close association. Stems are up to 5.0 mm in diam and have an apparently endarch dictyostele with scalariform metaxylem tracheids. Secondary xylem consists of tracheids with bordered pitting and uniseriate, parenchymatous rays 1–9 cells high. Leaves are arranged in a 3/8 pattern. They are small, pinnately-lobed, and vascularized by an U-shaped bundle. Distal to divergence, one of the apparent leaf traces becomes radial to resemble the base of a fertile structure. This implies a mode of attachment for the fructification and suggests evidence to interpret its homologies. The fertile specimen consists of laminae that diverge from a short stalk, and bifurcate distally. Laminae bear sporangia 0.6–0.7 mm in diam attached adaxially by vascularized pedicels. Spores average 36 μm in diam and are of the Kewaneesporites type. The combination of features now known for Cyathotheca exclude it from assignment to a currently-recognized major group of vascular plants, thus emphasizing that the Pennsylvanian coal swamp flora included a greater diversity than commonly is interpreted.     

THE RHIZOMORPH APEX OF PAURODENDRON; IMPLICATIONS FOR HOMOLOGIES AMONG THE ROOTING ORGANS OF LYCOPSIDA

A rhizomorph of Paurodendron with an intact apex recently has been discovered in Upper Pennsylvanian sediments of Ohio, and this provides the anatomical evidence necessary to interpret structure, ontogeny and homologies among lycophyte rooting organs. The basal meristem of Paurodendron is radial and lenticular, and produces an apical plug of parenchymatous tissue similar to a root cap. The plug is surrounded by a furrow associated with radially aligned cells that demonstrate a developmental correspondence to the furrow(s) of Isoetes. Based on external structural similarities at the rhizomorph apices of Paurodendron, Stigmaria, and young Nathorstiana, and on the anatomical similarities of Paurodendron to Isoetes, Stigmaria, Chaloneria, and Lepidocarpon embryos, all are interpreted as having a rooting organ that represents a modified shoot system that is fundamentally unlike the primary root system of seed plants. Likewise, the rootlets of rhizomorphic lycophytes are interpreted as leaves modified for rooting, and that have the equivalent of exogenous origin. As such, they are fundamentally unlike the adventitious roots of rhizomatous lycophytes like Lycopodium and Selaginella.     

Failure of low level gamma-irradiation of infective larvae to influence establishment or expulsion of Trichostrongylus colubriformis in guinea pigs

Trichostrongylus colubriformis infective larvae were subjected to various levels of γ-irradiation and administered to guinea pigs. The worms surviving were subsequently counted. Irradiation with 12.9 C kg⁻ inhibited worm establishment but lower doses neither influenced worm establishment nor survival.     

Suspected lysosomal storage disease in kangaroos

A probable neurovisceral lysosomal storage disease is reported, for the first time, in immature red and grey kangaroos (Macropus rufus and M. giganteus). Foamy, pale eosinophilic, periodic acid-Schiff positive, intracytoplasmic material was stored in the liver, lymphoid tissue, kidney, adrenal gland, stomach, blood vessels and central nervous system. Extensive Wallerian-type degeneration was present in the central nervous system. Electron microscopic study of one animal revealed electron dense, cytoplasmic lamellar bodies in neurons and foamy visceral cells. The disease differs from other reported storage diseases in the distribution and nature of the lesions.     

Metabolic and febrile responses to typhoid vaccine in humans: effect of beta-adrenergic blockade.

Fever and activation of acute phase responses were induced in human volunteers by intramuscular injection of typhoid vaccine. Vaccine injection caused a rapid (within 1 h) and sustained rise in metabolic rate (peak response 16%, 6-8 h), followed by later increases in white blood cell count (3-4 h), skin temperature (4-5 h), oral temperature (5-6 h), heart rate (6-8 h), and plasma cortisol (5-8 h). A peak fever [1.2 +/- 0.2 degree C (SE) rise] was recorded 12 h after vaccine injection. The involvement of the sympathetic nervous system in the development of these responses was investigated by the oral administration of propranolol before (80 mg) and 3 h after (40 mg) vaccine injection. Propranolol prevented the increases in metabolic rate, heart rate, and skin temperature but did not inhibit the rise in oral temperature or white cell count after vaccine administration. These data indicate that the sympathetic nervous system is responsible for the rise in energy expenditure associated with fever in humans. However, the rise in body temperature can develop in the absence of this increase in metabolic rate possibly by changes in heat loss.