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In the CNS, neurones are highly sensitive to the availability of oxygen. In conditions where oxygen availability is decreased, neuronal function can be altered, leading to injury and cell death. Hypoxia has been implicated in a number of central nervous system pathologies including stroke, head trauma and neurodegenerative diseases. Cellular responses to oxygen deprivation are complex and result in activation of short- and long-term mechanisms to conserve energy and protect cells. Failure of synaptic transmission can be observed within minutes following this hypoxia. The acute effects of hypoxia on synaptic transmission are primarily mediated by altering ion fluxes across membranes, pre-synaptic effects of adenosine and other actions at glutamatergic receptors. A more long-term feature of the response of neurones to hypoxia is the activation of transcription factors such as hypoxia-inducible factor. The activation of hypoxia-inducible factor is governed by a family of dioxygenases called hypoxia-inducible factor prolyl 4 hydroxylases ( PHDs). Under hypoxic conditions, PHD activity is inhibited, thereby allowing hypoxia-inducible factor to accumulate and translocate to the nucleus, where it binds to the hypoxia-responsive element sequences of target gene promoters. Inhibition of PHD activity stabilizes hypoxia-inducible factor and other proteins thus acting as a neuroprotective agent. This review will focus on the response of neuronal cells to hypoxia-inducible factor and its targets, including the prolyl hydroxylases. We also present evidence for acute effects of PHD inhibition on synaptic transmission and plasticity in the hippocampus. [ABSTRACT FROM AUTHOR]

The pro-inflammatory cytokine tumor-necrosis factor-α (TNF-α) is elevated in several neuropathological states that are associated with learning and memory deficits. Previous work has reported that TNF-α inhibits the induction of LTP in areas CA1 [Neurosci Lett 146 (1992) 176] and dentate gyrus [Neurosci Lett 203 (1996) 17]. The mechanism(s) underlying this process of inhibition have not to date been addressed. Here, we show that perfusion of TNF-α prior to long-term potentiation (LTP) inducing stimuli inhibited LTP, and that in late-LTP (3 h post-tetanus) a depression in synaptic field recordings was observed (68±5%, n=6 versus control 175±7%, n=6, P<0.001). We investigated the involvement of the mitogen-activated protein kinase (MAPK) p38 in the inhibition of LTP by TNF-α as p38 MAPK has previously been shown to be involved in interleukin-1β inhibition of LTP in the dentate gyrus [Neuroscience 93 (1999b) 57]. Perfusion of TNF-α led to an increase in the levels of phosphorylated p38 MAPK detectable in the granule cells of the dentate gyrus. The p38 MAPK inhibitor SB 203580 (1 μM) was found by itself to have no significant effect on either early or late phase LTP in the dentate gyrus. SB 203580 was found to significantly reverse the inhibition of early LTP by TNF-α (SB/TNF-α 174±5%, n=6 versus TNF-α 120±7%, n=6, P<0.001, 1 h post-tetanus) to values comparable to control LTP (control 175±7%, n=6). Interestingly however, the depressive effects of TNF-α on late LTP (2–3 h) were clearly not attenuated by p38 MAPK inhibition (SB/TNF-α 132±5%, n=6 versus control LTP 175±7%, n=6, P<0.001, 3 h post-tetanus). This work suggests that TNF-α inhibition of LTP represents a biphasic response, a p38 MAPK-dependent phase that coincides with the early phase of LTP and a p38 MAPK independent phase that temporally maps to late LTP. [Copyright &y& Elsevier]

Profiles mathematician and physicist Johann Benedict Listing. Personal and educational background; Contributions to topology.

We give necessary and sufficient conditions for the efficiency of the direct product of finitely many finite monogenic monoids. [ABSTRACT FROM AUTHOR]

The paper presents a theoretical model of the ankle joint, i.e. tibio-talar articulation, which shows how the articular surfaces and the ligaments, acting together as a mechanism, can control the passive kinematics of the joint. The authors had previously shown that, in virtually unloaded conditions, the ankle behaves as a single degree-of-freedom system, and that two ligament fibres remain nearly isometric throughout the flexion arc. Two different equivalent spatial parallel mechanisms together with corresponding kinematic models were formulated. These assumed isometricity of fibres within the calcaneal-fibular and tibio-calcaneal ligaments and rigidity of the articulating surfaces, taken as three sphere-plane contacts in one model, and as a single spherical pair in the other. Geometry parameters for the models were obtained from three specimens. Motion predictions compare quite well with the measured motion of the specimens. The differences are accounted for by the simplifications adopted to represent the complex anatomical structures, and might be reduced by future more realistic representations of the natural articular surfaces. [ABSTRACT FROM AUTHOR]

A finite semigroup S is said to be efficient if it can be defined by a presentation (A | R) with |R| -|A|=rank(H[sub 2] (S)). In this paper we demonstrate certain infinite classes of both efficient and inefficient semigroups. Thus, finite abelian groups, dihedral groups D[sub 2] [sub n] with n even, and finite rectangular bands are efficient semigroups. By way of contrast we show that finite zero semigroups and free semilattices are never efficient. These results are compared with some well-known results on the efficiency of groups. [ABSTRACT FROM AUTHOR]

Humans are better able to discriminate among human faces than faces of other species. This difference in perceptual discrimination is known as the “other-species effect”. Models of perception have posited that the ultimate functional significance of the other-species effect is a higher discrimination capability within an organism's most familiar and salient stimulus set while attenuating the ability to discriminate amongst unfamiliar stimuli. Here, human participants made masculinity judgements of human and macaque faces manipulated based on either human or macaque sexual dimorphism. Humans were more accurate at identifying masculine/feminine faces in species-congruent than species-incongruent transforms in both human and macaque faces. We observed an other-species effect whereby accuracy (correctly judging masculinized faces as more masculine) was highest for own-species faces. We also found that both men and women were better at judging the sex-typicality of male faces than female faces, regardless of the species of the face or the species of the manipulation. Our findings demonstrate an other-species effect for the perception of sex-typicality among human raters. [ABSTRACT FROM PUBLISHER]

Prior work has emphasized independent effects of voice pitch and apparent vocal tract length on women’s preferences for men’s voices. An interaction between the effects of pitch and apparent vocal tract length on male vocal attractiveness might be expected, however, given interactions between the effects of voice pitch and apparent vocal tract length on perceptions of body size, age, and sex. Here, we present empirical evidence for such an interaction. Women preferred low pitch in men’s voices more when associated with large vocal tracts than when associated with small vocal tracts and preferred large vocal tracts in men’s voices more when associated with low pitch than when associated with high pitch. Collectively, these findings demonstrate integration of different vocal cues in women’s mate preferences, potentially allowing women to better assess the quality of potential mates. [ABSTRACT FROM PUBLISHER]

Dopamine release is regulated by presynaptic dopamine receptors and interactions between adenosine and dopamine receptors have been well documented. In the present study, dopamine release from isolated striatal slices from Wistar rats was measured using fast cyclic voltammetry. Single-pulse stimulation (0.1 ms, 10 V) was applied every 5 min over a 2-h period. Superfusion with the adenosine (A)1 receptor agonist N6-cyclopentyladenosine (CPA), but not the A2 receptor agonist 3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino]ethyl] phenyl]propanoic acid (CGS 21680), inhibited dopamine release in a concentration-dependent manner (IC50 3.80 × 10−7 m; n = 10). The dose–response curve to CPA was shifted to the right (IC50 6.57 × 10−6 m; n = 6, P < 0.05 vs. control) by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Neither the D1 agonist 6-chloro-APB nor the D1 antagonist R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepine-7-ol (SCH 23390) altered dopamine release on their own. However, SCH 23390 (3 µm) significantly attenuated the response to CPA (IC50 1.44 × 10−5 m; n = 6, P < 0.01 vs. control). Furthermore, the inhibitory effect of CPA was significantly increased in the presence of 6-chloro-APB (1 µm). In radioligand binding experiments, CPA interacted with high- and low-affinity states of [3H]DPCPX-lableled A1 receptors. The high-affinity agonist binding to A1 receptors was inhibited by the stable guanosine triphosphate analogue Gpp(NH)p. In contrast, neither the proportion nor the affinity of high-affinity A1 receptors was altered by dopamine or SCH 23390. These results provide evidence that the inihibition of dopamine release by adenosine A1 receptors is dependent, at least in part, on the simultaneous activation of D1 dopamine receptors. While the mechanism underlying this interaction remains to be determined, it does not appear to involve an intramembrane interaction between A1 and D1 receptors. [ABSTRACT FROM AUTHOR]