Phylogenetic Diversity Indices from an Affine and Projective Viewpoint.

Phylogenetic diversity indices are commonly used to rank the elements in a collection of species or populations for conservation purposes. The derivation of these indices is typically based on some quantitative description of the evolutionary history of the species in question, which is often given in terms of a phylogenetic tree. Both rooted and unrooted phylogenetic trees can be employed, and there are close connections between the indices that are derived in these two different ways. In this paper, we introduce more general phylogenetic diversity indices that can be derived from collections of subsets (clusters) and collections of bipartitions (splits) of the given set of species. Such indices could be useful, for example, in case there is some uncertainty in the topology of the tree being used to derive a phylogenetic diversity index. As well as characterizing some of the indices that we introduce in terms of their special properties, we provide a link between cluster-based and split-based phylogenetic diversity indices that uses a discrete analogue of the classical link between affine and projective geometry. This provides a unified framework for many of the various phylogenetic diversity indices used in the literature based on rooted and unrooted phylogenetic trees, generalizations and new proofs for previous results concerning tree-based indices, and a way to define some new phylogenetic diversity indices that naturally arise as affine or projective variants of each other or as generalizations of tree-based indices.

The selective 5-HT6 receptor antagonist SLV has putative cognitive- and social interaction enhancing properties in rodent models of cognitive impairment.

In the present study, our aim was to investigate whether the novel highly selective 5-hydroxytryptamine6 (5-HT6) receptor antagonist SLV can ameliorate impairments in cognition and social interaction with potential relevance for both schizophrenia and Alzheimer's disease (AD). SLV sub-chronically - treated Wistar rats reared in isolation showed significantly enhanced prepulse inhibition (PPI) and object recognition performance when compared to vehicle - treated rats. In the isolated rats, also a significant reduction in expression of hippocampal neural cell adhesion molecule polysialylation (NCAM-PSA) was found which was ameliorated following treatment with SLV (30mg/kg). The social engagement deficit in rats exposed in utero (on gestational day 12.5) to valproic acid (VPA) was reversed by treatment with SLV (30mg/kg). SLV (20 and 30mg/kg, p.o.) fully reversed MK-801 - induced deficits in the ORT and also scopolamine - induced deficits in both the Object Recognition Task (ORT) and Object Location Task (OLT) in Wistar rats. In addition, a combination of sub-optimal doses of SLV and donepezil attenuated scopolamine-induced ORT deficits. Furthermore, SLV (10mg/kg, p.o.) reversed spontaneous alternation deficits in the T-maze induced by MK-801 administration in Swiss mice and in aged C57Bl/6J mice. SLV additionally improved T-Maze spatial learning and passive avoidance learning in Sprague-Dawley rats with amyoid-beta (Aß) injections into the hippocampus. In contrast, no benefits were found with SLV or the tested reference compounds (donepezil and RVT-101) on cognitive performance of 12months old Tg2576 mice. Also, in the social recognition task, an absence of cognitive enhancing properties was observed with SLV on "normal forgetting" in Wistar rats. Finally, analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) frequency recorded from pyramidal cells revealed a reduction in the presence of 1µM of SLV. In conclusion, SLV was investigated in several rodent animal models and found to be effective at a least effective dose (LED) of 20mg/kg and 10mg/kg (p.o.) in the rat and the mouse, respectively.

In vivo/ex vivo and behavioural study on central effects of 5-HT1B/1D and 5-HT1A antagonists in guinea pigs.

Serotonin 5-HT1A and 5-HT1B/1D receptors control serotonin (5-HT) release and are targets for the pharmacological treatment of psychiatric disorders. We investigated effects of the 5-HT1B/1D antagonist GR127935, the 5-HT1A antagonist WAY 100635 and a combination of both in guinea pigs on the behaviour in the forced swimming test and on extracellular 5-HT in the hippocampus and the prefrontal cortex using in vivo microdialysis. Tissue content of 5-HT, 5-HIAA and 5-HT turnover (ratio 5-HIAA/5-HT) were determined in a sample containing i) the median and dorsal raphe nuclei, ii) the frontal cortex, or iii) the ventral hippocampus ex vivo. BEHAVIOUR: Administration of WAY 100635 (0.3-3.0 mg/kg, i.p.) or GR127935 (1.0-10.0 mg/kg, i.p.) or the combination of both delayed immobility in the forced swim test. MICRODIALYSIS: Systemic administration of WAY 100635 (1 mg/kg i.p.), perfusion with GR127935 (10 microM perfused into the frontal cortex) in the medial prefrontal cortex or the combination of both treatments had no significant effect on extracellular 5-HT. 5-HT TISSUE CONTENT AND 5-HT TURNOVER IN THE TISSUE: Compared to controls, WAY 100635, GR127935 and the combination thereof, decreased cortical 5-HT (-30%), increased 5-HIAA and consequently 5-HT turnover in the cortex threefold and the raphe nuclei twofold. WAY 100635 decreased 5-HT in the hippocampus (-40%), too. WAY 100635 and GR127935 and their combination increased hippocampal 5-HIAA and 5-HT turnover twofold, compared to controls. The results suggest that both 5-HT1 antagonists have subtle effects on 5-HT function under resting conditions; combined treatment has no superior effects compared to solitary treatment.

Effects of exercise on plasma myosin heavy chain fragments and MRI of skeletal muscle.

The effects of a single series of high-force eccentric contractions involving the quadriceps muscle group (single leg) on plasma concentrations of muscle proteins were examined as a function of time, in the context of measurements of torque production and magnetic resonance imaging (MRI) of the involved muscle groups. Plasma concentrations of slow-twitch skeletal (cardiac beta-type) myosin heavy chain (MHC) fragments, myoglobin, creatine kinase (CK), and cardiac troponin T were measured in blood samples of six healthy male volunteers before and 2 h after 70 eccentric contractions of the quadriceps femoris muscle. Screenings were conducted 1, 2, 3, 6, 9, and 13 days later. To visualize muscle injury, MRI of the loaded and unloaded thighs was performed 3, 6, and 9 days after the eccentric exercise bout. Force generation of the knee extensors was monitored on a dynamometer (Cybex II+) parallel to blood sampling. Exercise resulted in a biphasic myoglobin release profile, delayed CK and MHC peaks. Increased MHC fragment concentrations of slow skeletal muscle myosin occurred in late samples of all participants, which indicated a degradation of slow skeletal muscle myosin. Because cardiac troponin T was within the normal range in all samples, which excluded a protein release from the heart (cardiac beta-type MHC), this finding provides evidence for an injury of slow-twitch skeletal muscle fibers in response to eccentric contractions. Muscle action revealed delayed reversible increases in MRI signal intensities on T2-weighted images of the loaded vastus intermedius and deep parts of the vastus lateralis. We attributed MRI signal changes due to edema in part to slow skeletal muscle fiber injury.(ABSTRACT TRUNCATED AT 250 WORDS)

The dopamine D3 receptor partial agonist, BP 897, is an antagonist at human dopamine D3 receptors and at rat somatodendritic dopamine D3 receptors.

Recent studies have fueled the interest in dopamine D3 receptor antagonists and partial agonist for the treatment of psychosis and drug abuse, respectively. N-[4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl]naphthalene-2-carboxamide (BP 897) is a dopamine D3 receptor selective ligand recently described as partial agonist with potential effects on drug-dependence. The aim of the present study was to determine both the functional activity of BP 897 at human dopamine D3 receptors expressed in Chinese hamster ovary (CHO) cells and in an electrophysiological in vivo model of dopaminergic activity. BP 897 failed to stimulate the human dopamine D3 receptor and showed antagonistic effects (cpIC(50)=9.51) in a [(35)S]GTPgammaS binding assay in cells expressing the human dopamine D3 receptor. In vivo, BP 897 up to 8.2 mg/kg, i.v., had no agonistic effects on firing rate of substantia nigra dopaminergic neurons and antagonized the quinpirole-induced inhibition of firing (DID(50)=1.1 mg/kg). Our data demonstrate that BP 897 acts, in vivo and in vitro, as a dopamine D3 receptor antagonist.

Localisation of mRNA for h5-HT1B and h5-HT1D receptors in human dorsal raphe.

In the mammalian mesencephalon, virtually all serotoninergic neurons are located in the raphe nuclei and the adjacent reticular formation. Pharmacological evidence obtained in rodents suggests that terminal and somatodendritic autoreceptors controlling serotonin (5-hydroxytryptamine, 5-HT) release belong to the 5-HT1B/D subtype of receptors, whereas somatodendritic autoreceptors controlling neuronal cell firing are predominantly of the 5-HT1A subtype. This study investigated the presence of h5-HT1D and h5-HT1B receptor mRNA within the subdivisions of the dorsal raphe of post-mortem human brains by means of in situ hybridisation. Although differences in the labelling intensity, which may be caused by different pre- and/or post-mortem conditions, were obvious among the specimens, all brains expressed both the h5-HT1D and the h5-HT1B mRNA in dorsal raphe neurons. In comparison to h5-HT1D mRNA, expression of h5-HT1B mRNA was slightly more abundant. Information on the existence and localisation of h5-HT1D and h5-HT1B receptors in human dorsal raphe neurons confirms that both subtypes may serve an autoreceptor function in humans. This finding is of pharmacological relevance since these receptors are potential new targets for therapeutic interventions in psychiatric disorders such as depression and anxiety.

Cine-MR in dissection of the thoracic aorta.

Magnetic resonance imaging (MRI) of the thoracic aorta, including cine-MRI, was performed in 25 patients suspected of having dissection of the thoracic aorta. MRI was correlated with echocardiography, CT and angiography. The sensitivity of MRI (100%) was most closely followed by CT and angiography (83% and 77% respectively). The specificity of MRI and angiography was equally good, at 100% each. MRI was able to demonstrate the intimal flap in all 9 cases of aortic dissection, and there were no false-positive results. Differentiation of thrombosis and slow flow was possible on proton density images, gradient echo images permitted detection of the entry and re-entry sites. The nature of the dissection was determinated correctly in 8 out of 9 cases. MRI is capable of providing all the relevant parameters necessary to decide appropriate treatment of dissecting aneurysms of the thoracic aorta.

[Diagnosis and staging of blunt kidney trauma. A comparison of urinalysis, i.v. urography, sonography and computed tomography]. / Diagnose und Staging von stumpfen Nierentraumen. Vergleich von Harnanalyse, i.v. Urographie, Sonographie und Computertomographie.

In a retrospective study of 1230 patients with blunt abdominal or flank trauma, the results of microscopic urinalysis, urography, sonography, and computed tomography in the diagnosis and staging of renal injuries were compared. Haematuria was present in 98% of renal lacerations and in all pedicle injuries, whereas among 1038 patients without haematuria only one small laceration was found. The degree of haematuria showed no correlation with the severity of renal injury. 92 renal injuries were diagnosed radiologically, including 58 lacerations, 31 contusions, and three pedicle injuries. Computed tomography was performed in 39 lacerations and six contusions, and allowed correct diagnosis and staging in all cases. Urography established the correct diagnosis in 72%, and sonography in 85%. Sensitivity in the diagnosis of clinically relevant injuries (lacerations and pedicle injuries) was 98% (specificity: 99%), when both modalities were combined. Based on the results of our study, we suggest the use of sonography as a screening modality in blunt abdominal or flank trauma, and additional urography in case of haematuria. Computed tomography is the method of choice for exact staging of suspected renal injury.

[Space-occupying lesions of the pineal region in magnetic resonance tomography]. / Raumforderungen der Pinealisregion in der Magnetresonanztomographie.

Preoperative CT and MRI studies of 24 patients with space-occupying lesions of the pineal region were analysed. MRI demonstrated all 24 lesions, whereas CT could detect only 20 out of 24. MRI was superior to CT in assessment of size, localisation and relation to adjacent structures. No significant difference was found between CT and MRI in preoperative prediction of tumour histology.

[The value of CT and MRT in assessing aortocoronary venous bypasses in comparison with coronary angiography]. / Die Wertigkeit von CT und MRT bei der Erfassung von aortokoronaren Venenbrücken im Vergleich zur Koronarangiographie.

In a follow-up study of 20 patients with a total of 52 aortocoronary venous bypass grafts (ACVB) three months after surgery, the patency of the grafts was assessed by magnetic resonance tomography (MR) followed by contrast enhanced CT-scan and selective coronary angiography on the following day. Each examination was interpreted independently and immediately after the procedure for the visibility and patency of the grafts. The statistical figures for the non-occluded grafts showed a sensitivity of 90.24% and a specificity of 54.54% for the CT scans and a sensitivity of 73.17% with a specificity of 72.72% for the MR. Although the sensitivity of the CT is somewhat higher than that of MR, neither procedure offers a clear advantage over each other and neither of both methods alone is adequate for the assessment of ACVB's. They are therefore only valuable as an adjunct to clinical data and as a screening procedure for selective coronary angiography.

[Magnetic resonance tomography of the craniocervical junction in chronic polyarthritis]. / Magnetresonanztomographie des kranio-zervikalen Uberganges bei chronischer Polyarthritis.

Magnetic resonance imaging and conventional radiographs and tomograms were correlated in 61 patients with chronic polyarthritis. Radiographs of the occipito-cervical junction only demonstrated bone lesions, erosions were detected on conventional tomograms. MRI was adequate for demonstration of bone abnormalities and soft tissue lesion and was especially suitable for detection of complications at the cervical spinal cord.

Inhibition of calpain prevents NMDA-induced cell death and beta-amyloid-induced synaptic dysfunction in hippocampal slice cultures.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is a multifactorial, neurodegenerative disease, which is in part caused by an impairment of synaptic function, probably mediated by oligomeric forms of amyloid-beta (Abeta). While the Abeta pathology mainly affects the physiology of neurotransmission, neuronal decline is caused by excitotoxic cell death, which is mediated by the NMDA receptor. A comprehensive therapeutic approach should address both Abeta-induced synaptic deficits, as well as NMDA receptor-mediated neurodegeneration, via one molecular target. This study was designed to test whether calpain could be involved in both pathological pathways, which would offer a promising avenue for new treatments. EXPERIMENTAL APPROACH: Application of the specific, water-soluble calpain inhibitor A-705253 was used to inhibit calpain in hippocampal slice cultures. We examined whether inhibition of calpain would prevent Abeta-induced deficits in neurotransmission in CA1, as well as NMDA-induced neuronal cell death. KEY RESULTS: A-705253 dose-dependently prevented excitotoxicity-induced neurodegeneration at low nanomolar concentrations, determined by propidium iodide histochemistry. Inhibition of the NMDA receptor similarly protected from neuronal damage. Caspase staining indicated that calpain inhibition was protective by reducing apoptosis. Electrophysiological analysis revealed that inhibition of calpain by A-705253 also fully prevented Abeta oligomer-induced deficits in neurotransmission. The protective effect of calpain was compared to the clinically available NMDA receptor antagonist memantine, which was also effective in this model. CONCLUSIONS AND IMPLICATIONS: We suggest that inhibition of calpain exhibits a promising strategy to address several aspects of the pathology of AD that may go beyond the available therapeutic intervention by memantine.

Synaptic transmission is impaired prior to plaque formation in amyloid precursor protein-overexpressing mice without altering behaviorally-correlated sharp wave-ripple complexes.

One of the hallmarks of Alzheimer's disease is the accumulation of amyloid plaques in brains of affected patients. Several recent studies provided evidence that soluble oligomer forms of amyloid-beta (Abeta) rather than plaques determine cognitive decline. In vitro studies using artificial Abeta oligomer preparations suggest that such pathophysiology is caused by a specific impairment of synaptic function. We examined whether synaptic deficits occur before deposition of insoluble fibrillar Abeta by analyzing brain slices taken from young Tg2576 mice overexpressing mutant amyloid precursor protein. Excitatory synaptic transmission in the hippocampal CA1 region was strongly impaired before plaque development, suggesting a dissociation of an early synaptic impairment, probably caused by soluble oligomeric amyloid-beta, from subsequent plaque formation. At higher age neurotransmission was also decreased in wild type mice, paralleling a cognitive decline of normal aged animals. Memory formation in rats is accompanied by distinct hippocampal network oscillations. It has recently been shown that hippocampal gamma oscillations, a network correlate of exploratory behavior, are impaired in amyloid precursor protein (APP)-overexpressing mice. We determined whether sharp wave-ripple complexes, which contribute to memory consolidation during slow wave-sleep, are modified in Tg2576 mice. Interestingly, neither sharp waves nor superimposed ripples were changed at pre-plaque or plaque stages. During aging, however, there was a strong reduction of sharp wave frequency and ripple energy in wild type and APP-overexpressing animals. This indicates that the reported changes in network oscillations following APP-overexpression are specific for gamma oscillations, whereas aging has a more general effect on network properties. Taken together our data suggest that non-fibrillar forms of Abeta--possibly Abeta oligomers--specifically interfere with synaptic function in Tg2576, but do not globally alter memory-related network properties. We propose that mechanisms leading to Abeta-related cognitive decline are different from those related to aging.

Subtotal rarefication of one aortic leaflet in a bicuspid aortic valve due to large aneurysm of left Valsalva's sinus.

In a 39-year-old man an isolated, unruptured extracardiac aneurysm of the left sinus of Valsalva led to almost complete rarefication of one aortic valve leaflet, causing insufficiency of the valve. At operation the aneurysm entrance was closed with a patch and prosthetic replacement of the bicuspid aortic valve was performed. The result was satisfactory.

[Osteopoikilosis in magnetic resonance tomography (case report)]. / Osteopoikilie in der Magnetresonanztomographie (Fallbericht).

A case report shows the differential diagnosis of osteopoikilosis ("spotted bones")--beside X-ray and scintigraphic results--in Magnetic Resonance Imaging (MRI).

Light concentric exercise and heavy eccentric muscle loading: effects on CK, MRI and markers of inflammation.

The consequences of a single bout of heavy eccentric exercise with and without repeated concentric exercises on MRI images, serum CK levels and markers of inflammation were studied. Two groups (ECC and ECCON), each consisting of 18 male volunteers, performed 70 eccentic contractions of the quadriceps femoris muscle. The study group (ECCON) performed additional concentric contractions on a dynamometer (Cybex II+) one day before and two hours, 1, 2, 3, 6 and 9 days after eccentric loading. Serum levels of creatine kinase (CK) were examined as a function of time, and correlated with measurements of magnetic resonance imaging (MRI) of the involved muscle groups. T2-weighted images of the thigh muscles were studied. Serum C-reactive protein, complement factors C3c and C4, haptoglobin and transferrin were measured as markers of inflammation. Additional concentric contractions (ECCON group) significantly increased CK, compared to the ECC group. However, it has no apparent effect on MRI signal intensity changes, which were of equal magnitude in the loaded vastus intermedius and deep parts of the vastus lateralis in both groups. Likewise, the serum markers of inflammation of the exercised muscles appeared to be absent. Based on MRI-images, additional concentric contractions had no statistically significant effect on muscle damage and breakdown of connective tissue. The five-fold increase in CK in the ECCON group could be a reflection of "massaging out" of the CK from the muscles into the circulation by additional concentric exercises. However, it could also be an indication for a superior sensitivity of assessing muscle fiber damage in comparison to the MRI.

[The prone position in ARDS. A successful therapeutic strategy]. / Bauchlagerung im ARDS. Ein erfolgversprechender therapeutischer Ansatz.

As early as 1974, Brian advocated the prone position for ventilated patients. He suggested that this position might enhance ventilation of the dorsal parts of the lungs, thereby improving oxygenation. These considerations have been confirmed by several experimental and clinical studies. Better secretion removal, decreased intrapulmonary shunting, and an increased FRC are thought to be responsible for the observed improvement of oxygenation. However, the prone position never became very popular in the clinical treatment of the adult respiratory distress syndrome (ARDS). Routine performance of thoracic CT scans in ARDS patients demonstrated preferential distribution of pathological densities in the dependent lung areas. The prone position therefore could possibly benefit these patients, as shown by two recent studies. The aim of our study was to evaluate the influence of repeatedly turning the patient to the prone position on gas exchange and thoracic CT findings in multiple-trauma patients. METHODS. Seven ventilated intensive care patients with severe ARDS (Murray Score > 2.5, Quotient > 0.7, mean airway pressure > 18 cm H2O, thoracic CT scan showing dorsal atelectases) were included in the study. Patients were turned from the supine to the prone position at 12-h intervals using an air-cushion bed (Mediscus, Austria). Redistribution of dystelectatic or atelectatic dependent lung areas was verified by means of repeated thoracic CT scans (Figs. 1, 8). RESULTS. The patients were intermittently turned for 6.5 +/- 1.1 days. The course of gas exchange is shown in Figs. 2 and 3. Initially, improvement of the respiratory quotient could only be achieved during prone positioning, from the 2nd day in the supine position as well. Intrapulmonary shunting showed a similar trend (Figs. 4 and 5). No significant changes in cardiovascular parameters could be observed. Control thoracic CT scans showed uniform reduction of atelectases in dependent lung areas (Figs. 1 and 8). The inspiratory fraction of oxygen could be reduced significantly as of the 2nd day (Fig. 7). Constant levels of positive end-expiratory pressure and tidal volume were associated with decreasing mean and plateau airway pressures (Fig. 6). DISCUSSION. Repeatedly turning the patient to the prone position produced long-lasting improvement of arterial oxygenation, which persists up to the end of the weaning process. This is in good accordance with other studies, however, this is the first study to report an observation period of more than 6 days of repeatedly turning the patient. These positive effects on gas exchange can be attributed to sudden improvement of the ventilation-perfusion ratio within the lung areas that become dependent after turning to the prone position. Due to reduced hydrostatic pressure and relative hyperventilation, previously collapsed alveoli are recruited in the lung areas that become non-dependent after turning to the prone position.