Time course of biological activity in fresh murine osteochondral allografts paralleled to the recipient's immune response

The use of fresh osteochondral allografts is a popular approach to treat articular cartilage lesions. Immunological reactions of the recipient elicited by the allograft's osseous portion, however, frequently result in their deterioration. So far, little emphasis has been put on describing morphology and biological activity in fresh allografts and paralleling these to the immunological processes triggered in the host. Therefore, in the present study murine neonatal femora, serving as osteochondral grafts, were transplanted as fresh isografts (controls) or allografts (the latter in non- or presensitized mice) and retrieved after 2, 5, 10, and 20 days. It was shown that (1) in isografts active bone cells (osteoblasts, osteoclasts) were present, the bone marrow was repopulated with hematopoietic cells, the diaphysis increased in length, and no specific immunological reaction by the recipient was evoked. (2) Allografts transplanted into nonsensitized hosts initially appeared similar as isografts, but activated T lymphocytes at the transplantation site preceded loss of active bone cells within the graft and development of fibrosis within the marrow cavity. (3) In allografts transplanted into presensitized recipients, severe deterioration of the graft was observed with very few active bone cells, accompanied by an invasion of T lymphocytes and fibrosis in the marrow cavity already in early stages. Similar to vital organ transplantation, the function of cells within osteochondral allografts is severely impaired after being recognized by the immune system. Therefore, emphasis has to be placed on the development of procedures preserving cartilage biology while reducing the antigenicity of the allograft's osseous portion.

Characterization of three human sec14p-like proteins: alpha-tocopherol transport activity and expression pattern in tissues

Three closely related human sec14p-like proteins (hTAP1, 2, and 3, or SEC14L2, 3, and 4, respectively) have been described. These proteins may participate in intracellular lipid transport (phospholipids, squalene, tocopherol analogues and derivatives) or influence regulatory lipid-dependent events. Here, we show that the three recombinant hTAP proteins associate with the Golgi apparatus and mitochondria, and enhance the in vitro transport of radioactively labeled alpha-tocopherol to mitochondria in the same order of magnitude as the human alpha-tocopherol transfer protein (alpha-TTP). hTAP1 and hTAP2 are expressed in several cell lines, whereas the expression level of hTAP3 is low. Expression of hTAP1 is induced in human umbilical cord blood-derived mast cells upon differentiation by interleukin 4. In tissues, the three hTAPs are detectable ubiquitously at low level; pronounced and localized expression is found for hTAP2 and hTAP3 in the perinuclear region in cerebellum, lung, liver and adrenal gland. hTAP3 is well expressed in the epithelial duct cells of several glands, in ovary in endothelial cells of small arteries as well as in granulosa and thecal cells, and in testis in Leydig cells. Thus, the three hTAPs may mediate lipid uptake, secretion, presentation, and sub-cellular localization in a tissue-specific manner, possibly using organelle- and enzyme-specific docking sites.

Orbital changes, variation in solar activity and increased anthropogenic activities: controls on the Holocene flood frequency in the Lake Ledro area, Northern Italy

Adding to the on-going debate regarding vegetation recolonisation (more particularly the timing) in Europe and climate change since the Lateglacial, this study investigates a long sediment core (LL081) from Lake Ledro (652ma.s.l., southern Alps, Italy). Environmental changes were reconstructed using multiproxy analysis (pollen-based vegetation and climate reconstruction, lake levels, magnetic susceptibility and X-ray fluorescence (XRF) measurements) recorded climate and land-use changes during the Lateglacial and early-middle Holocene. The well-dated and high-resolution pollen record of Lake Ledro is compared with vegetation records from the southern and northern Alps to trace the history of tree species distribution. An altitudedependent progressive time delay of the first continuous occurrence of Abies (fir) and of the Larix (larch) development has been observed since the Lateglacial in the southern Alps. This pattern suggests that the mid-altitude Lake Ledro area was not a refuge and that trees originated from lowlands or hilly areas (e.g. Euganean Hills) in northern Italy. Preboreal oscillations (ca. 11 000 cal BP), Boreal oscillations (ca. 10 200, 9300 cal BP) and the 8.2 kyr cold event suggest a centennial-scale climate forcing in the studied area. Picea (spruce) expansion occurred preferentially around 10 200 and 8200 cal BP in the south-eastern Alps, and therefore reflects the long-lasting cumulative effects of successive boreal and the 8.2 kyr cold event. The extension of Abies is contemporaneous with the 8.2 kyr event, but its development in the southern Alps benefits from the wettest interval 8200-7300 cal BP evidenced in high lake levels, flood activity and pollen-based climate reconstructions. Since ca. 7500 cal BP, a weak signal of pollen-based anthropogenic activities suggest weak human impact. The period between ca. 5700 and ca. 4100 cal BP is considered as a transition period to colder and wetter conditions (particularly during summers) that favoured a dense beech (Fagus) forest development which in return caused a distinctive yew (Taxus) decline.We conclude that climate was the dominant factor controlling vegetation changes and erosion processes during the early and middle Holocene (up to ca. 4100 cal BP).

Baclofen and gamma-hydroxybutyrate differentially altered behavior, EEG activity and sleep in rats.

OBJECTIVES Animal and human studies have shown that sleep may have an impact on functional recovery after brain damage. Baclofen (Bac) and gamma-hydroxybutyrate (GHB) have been shown to induce physiological sleep in humans, however, their effects in rodents are unclear. The aim of this study is to characterize sleep and electroencelphalogram (EEG) after Bac and GHB administration in rats. We hypothesized that both drugs would induce physiological sleep. METHODS Adult male Sprague-Dawley rats were implanted with EEG/electromyogram (EMG) electrodes for sleep recordings. Bac (10 or 20 mg/kg), GHB (150 or 300 mg/kg) or saline were injected 1 h after light and dark onset to evaluate time of day effect of the drugs. Vigilance states and EEG spectra were quantified. RESULTS Bac and GHB induced a non-physiological state characterized by atypical behavior and an abnormal EEG pattern. After termination of this state, Bac was found to increase the duration of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep (∼90 and 10 min, respectively), reduce sleep fragmentation and affect NREM sleep episode frequency and duration (p<0.05). GHB had no major effect on vigilance states. Bac drastically increased EEG power density in NREM sleep in the frequencies 1.5-6.5 and 9.5-21.5 Hz compared to saline (p<0.05), while GHB enhanced power in the 1-5-Hz frequency band and reduced it in the 7-9-Hz band. Slow-wave activity in NREM sleep was enhanced 1.5-3-fold during the first 1-2 h following termination of the non-physiological state. The magnitude of drug effects was stronger during the dark phase. CONCLUSION While both Bac and GHB induced a non-physiological resting state, only Bac facilitated and consolidated sleep, and promoted EEG delta oscillations thereafter. Hence, Bac can be considered a sleep-promoting drug and its effects on functional recovery after stroke can be evaluated both in humans and rats.

The Influence of Pre-stimulus EEG Activity on Reaction Time During a Verbal Sternberg Task is Related to Musical Expertise

Abstract Previous work highlighted the possibility that musical training has an influence on cognitive functioning. The suggested reason for this influence is the strong recruitment of attention, planning, and working memory functions during playing a musical instrument. The purpose of the present work was twofold, namely to evaluate the general relationship between pre-stimulus electrophysiological activity and cognition, and more specifically the influence of musical expertise on working memory functions. With this purpose in mind, we used covariance mapping analyses to evaluate whether pre-stimulus electroencephalographic activity is predictive for reaction time during a visual working memory task (Sternberg paradigm) in musicians and non-musicians. In line with our hypothesis, we replicated previous findings pointing to a general predictive value of pre-stimulus activity for working memory performance. Most importantly, we also provide first evidence for an influence of musical expertise on working memory performance that could distinctively be predicted by pre-stimulus spectral power. Our results open novel perspectives for better comprehending the vast influences of musical expertise on cognition.

Physiological time structure of the tibialis anterior motor activity during sleep in mice, rats and humans

The validation of rodent models for restless legs syndrome (Willis-Ekbom disease) and periodic limb movements during sleep requires knowledge of physiological limb motor activity during sleep in rodents. This study aimed to determine the physiological time structure of tibialis anterior activity during sleep in mice and rats, and compare it with that of healthy humans. Wild-type mice (n = 9) and rats (n = 8) were instrumented with electrodes for recording the electroencephalogram and electromyogram of neck muscles and both tibialis anterior muscles. Healthy human subjects (31 ± 1 years, n = 21) underwent overnight polysomnography. An algorithm for automatic scoring of tibialis anterior electromyogram events of mice and rats during non-rapid eye movement sleep was developed and validated. Visual scoring assisted by this algorithm had inter-rater sensitivity of 92-95% and false-positive rates of 13-19% in mice and rats. The distribution of the time intervals between consecutive tibialis anterior electromyogram events during non-rapid eye movement sleep had a single peak extending up to 10 s in mice, rats and human subjects. The tibialis anterior electromyogram events separated by intervals <10 s mainly occurred in series of two-three events, their occurrence rate in humans being lower than in mice and similar to that in rats. In conclusion, this study proposes reliable rules for scoring tibialis anterior electromyogram events during non-rapid eye movement sleep in mice and rats, demonstrating that their physiological time structure is similar to that of healthy young human subjects. These results strengthen the basis for translational rodent models of periodic limb movements during sleep and restless legs syndrome/Willis-Ekbom disease.