KDM6B-dependent chromatin remodeling underpins effective virus-specific CD8+ T cell differentiation

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Microclimate in hollow trees and how it affects an inhabiting beetle species,Osmoderma eremita

1. Studies of species' responses to microclimatic conditions have increased our understanding of their habitat requirements and possible responses to climate warming. However, little is known about the role of microclimate for insects inhabiting hollow trees.
2. We explored the relationship between tree characteristics and microclimate, and analysed how the microclimate in tree-hollows affects the occurrence and body size of an endangered beetle species, Osmoderma eremita.
3. We placed temperature data-loggers in wood mould (= loose material in tree-hollows) and surveyed O. eremita in 47 hollows in oak pastures in south-eastern Sweden. We found that tree characteristics previously known to be associated with occurrence of beetle species confined to tree-hollows (larger diameters, more wood mould, entrances higher up, and not directed upwards) tend to decrease moisture and moisture variation, while their effects on temperature and temperature fluctuations differ during different seasons. This indicates that microclimatic conditions are important for beetles in hollow trees, and many specialised species seem to avoid conditions that are too moist.
4. O. eremita occurred more frequently in trees with a warmer and more stable microclimate, while adult body size decreased with a warmer microclimate. A positive effect of a warmer microclimate was expected, since the study was done near the northern margin of the species' range.
5. O. eremita is confined to living in hollow trees, which may be due to the microclimate there being more stable in comparison to both the ambient climate and the microclimate in standing and downed dead wood.

     

Rat neurophysiological taste responses to salt solutions

1. Neurophysiological studies on the chemoresponsive tongueunits of the rat geniculate ganglion readily detected and furthercharacterized the two major functional neural groups designatedas ‘acid’ and ‘salt’ units by otherinvestigators in chorda tympani recordings. Units belongingto either of these groups were initially identified on the basisof their responses to a series of chemical solutions (a TestSeries) developed to distinguish unit groups in the geniculateganglion of the cat, dog and goat. 2. The nature of active ionicspecies effective in stimulating the units of the two differentgroups was further elaborated by studying their responses toa variety of salt solutions. From these studies, it was concludedthat the optimum molecular species for the acid units is anacid, where an acid is defined as a Br0nsted acid or protondonating molecule. A variety of molecular species may be activein solution, including some nitrogen compounds. Responses tosalt solutions by acid units are determined in part by the actionof the cation functioning as a Brønsted acid (NH₄), orin promoting proton donor molecules in water (mainly H₃O⁺).The salt units, on the other hand, are almost exclusively responsiveto solutions containing Na ⁺ and Li⁺. All other solutions werevirtually inactive. It was concluded that under a wide varietyof environmental conditions, Na+ would be the exclusive stimulusfor the salt units. Na⁺ and Li⁺ were found to be highly stimulatingwhen accompanied by a wide variety of solute anions, althoughthose containing the halogens (Cl^–, F^–, I^–,Br^–) were among the most stimulatory compounds tested.3. The establishment that the stimulus is a proton donor moleculefor the acid units and the Na⁺ and Li⁺ for the salt units hasprofound theoretical implications for the taste receptor. Biophysicalmodels of taste receptors are reviewed with respect to thisimproved understanding of the stimuli for the two types of units.It is suggested, after consideration of certain basic biochemicalaspects of the situation, that the acid receptor (possibly animidazole group) forms, as part of a protein, a proton conductingcircuit for driving an intracellular energy process devotedto proton sensing transmission. It is further suggested, inlight of the extreme specificity shown to Na ⁺, that receptorattachment is of the multidentate ligand variety and is probablylinked to Na⁺, K⁺ transport across the cell membrane, as proposedby DeSimone et al. (1981).     

Sequence Analysis of a DNA Fragment from Buchnera aphidicola (Aphid Endosymbiont) Containing the Genes dapD-htrA-ilvI-ilvH-ftsL-ftsI-murE

Buchnera aphidicola is a prokaryotic endosymbiont of the aphid Schizaphis graminum. One of the endosymbiont's functions is the synthesis of branched-chain amino acids. A 9.7-kilobase B. aphidicola chromosomal DNA fragment was cloned and sequenced and found to contain genes encoding acetohydroxy acid synthase (ilvIH), the first enzyme of the parallel pathway of isoleucine and valine biosynthesis. Previously we have detected ilvC and ilvD, encoding the two other enzymes of this pathway. In addition the DNA fragment contained genes for cell division (ftsL, ftsI), murein biosynthesis (murE), lysine biosynthesis (dapD) and a periplasmic protease (htrA). In these properties B. aphidicola resembles free-living bacteria. Received: 25 April 1998 / Accepted: 28 April 1998     

One-year longitudinal evaluation of sensorimotor functions in APP751SL transgenic mice

Intracerebral amyloid-beta (Aβ) peptide deposition is considered to play a key role in Alzheimer's disease and is designated as a principal therapeutic target. The relationship between brain Aβ levels and clinical deficits remains, however, unclear, both in human patients and in animal models of the disease. The purpose of the present study was to investigate, in a transgenic mouse model of brain amyloidosis, the consequences of Aβ deposition on basic neurological functions using a longitudinal approach. Animals were phenotyped at different ages corresponding to graded neuropathological stages (from no extracellular Aβ deposition to high amyloid loads). Sensory functions were evaluated by assessing visual and olfactory abilities and did not show any effects of the amyloid precursor protein (APP) transgene. Motor functions were assessed using multiple experimental paradigms. Results showed that motor strength was considerably reduced in APP transgenic mice compared with control animals. No deficit was noted in a motor coordination test although APP transgenic mice displayed decreased locomotion on a stationary beam. Hypolocomotion was also observed in the standard open-field test. Measures of anxiety obtained in the elevated plus-maze show some evidence of hyperanxiety in 15-month-old transgenic mice. Some of the neurological impairments showed by APP mice had an early onset and worsened with progressive aging, in parallel to gradual accumulation of Aβ in brain parenchyma. Relationships between neuropathologically assessed amyloid loads and behavioral deficits were further explored, and it was observed that motor strength deficits were correlated with cortical amyloid burden.     

Cartilage stress-relaxation proceeds slower at higher compressive strains

Articular cartilage is the connective tissue which covers bone surfaces and deforms during in vivo activity. Previous research has investigated flow-dependent cartilage viscoelasticity, but relatively few studies have investigated flow-independent mechanisms. This study investigated polymer dynamics as an explanation for the molecular basis of flow-independent cartilage viscoelasticity. Polymer dynamics predicts that stress-relaxation will proceed more slowly at higher volumetric concentrations of polymer. Stress-relaxation tests were performed on cartilage samples after precompression to different strain levels. Precompression increases the volumetric concentration of cartilage biopolymers, and polymer dynamics predicts an increase in relaxation time constant. Stress-relaxation was slower for greater precompression. There was a significant correlation between the stress-relaxation time constant and cartilage volumetric concentration. Estimates of the flow-dependent timescale suggest that flow-dependent relaxation occurs on a longer timescale than presently observed. These results are consistent with polymer dynamics as a mechanism of cartilage viscoelasticity.     

Effects of the calcium antagonist, diltiazem on in vitro and in vivo/in vitro bone resorption

The effect of the calcium antagonist diltiazem on bone resorption in organ culture has been investigated. It was found that diltiazem was ineffective alone but that in concentrations above 5 mumol/l it reduced mineral and organic resorption induced in vitro by 1.25 dihydroxycholecalciferol (1.25 (OH)2D3). No additivity with calcitonin effects was observed. Diltiazem did not significantly affect bone resorbing activity stimulated by 24,25(OH)2D3. Bone resorption was measured by an in vivo/in vitro technique using 45Ca prelabelled mice. Compared with 1.25(OH)2D3 alone treated group (0.480 pmol/g), it was found that diltiazem (100 nmol/g) reduced bone resorption without effect on calcium and phosphorus plasmatic concentrations at death. These data suggest that such a calcium antagonist is able to inhibit 1.25-(OH)2D3-increased-bone resorption either in vitro or in vivo/in vitro.     

Synthesis, SAR and in vivo activity of novel thienopyridine sulfonamide pyrrolidinones as factor Xa inhibitors.

Thienopyridine sulfonamide pyrrolidinones were found to be potent and selective inhibitors of the coagulation cascade enzyme factor Xa. SAR studies led to several compounds that were selected for further in vivo investigation. These novel aryl binding pocket moieties represent a structural modification to a series of fXa inhibitors. Several compounds proved to be efficacious i.v. antithrombotic agents.     

MiR-690, an exosomal-derived miRNA from M2-polarized macrophages,improves insulin sensitivity in obese mice

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