Shell Neurons of the Master Circadian Clock Coordinate the Phase of Tissue Clocks Throughout the Brain and Body

Background: Daily rhythms in mammals are programmed by a master clock in the suprachiasmatic nucleus (SCN). The SCN contains two main compartments (shell and core), but the role of each region in system-level coordination remains ill defined. Herein, we use a functional assay to investigate how downstream tissues interpret region-specific outputs by using in vivo exposure to long day photoperiods to temporally dissociate the SCN. We then analyze resulting changes in the rhythms of clocks located throughout the brain and body to examine whether they maintain phase synchrony with the SCN shell or core. Results: Nearly all of the 17 tissues examined in the brain and body maintain phase synchrony with the SCN shell, but not the SCN core, which indicates that downstream oscillators are set by cues controlled specifically by the SCN shell. Interestingly, we also found that SCN dissociation diminished the amplitude of rhythms in core clock gene and protein expression in brain tissues by 50–75 %, which suggests that light-driven changes in the functional organization of the SCN markedly influence the strength of rhythms in downstream tissues. Conclusions: Overall, our results reveal that body clocks receive time-of-day cues specifically from the SCN shell, which may be an adaptive design principle that serves to maintain system-level phase relationships in a changing environment. Further, we demonstrate that lighting conditions alter the amplitude of the molecular clock in downstream tissues, which uncovers a new form of plasticity that may contribute to seasonal changes in physiology and behavior

Language complexity in on-line health information retrieval

The number of people searching for on-line health information has been steadily growing over the years so it is crucial to understand their specific requirements in order to help them finding easily and quickly the specific in-formation they are looking for. Although generic search engines are typically used by health information seekers as the starting point for searching information, they have been shown to be limited and unsatisfactory because they make generic searches, often overloading the user with the provided amount of results. Moreover, they are not able to provide specific information to different types of users. At the same time, specific search engines mostly work on medical literature and provide extracts from medical journals that are mainly useful for medical researchers and experts but not for non-experts. A question then arises: Is it possible to facilitate the search of on-line health/medical information based on specific user requirements? In this pa-per, after analysing the main characteristics and requirements of on-line health seeking, we provide a first answer to this question by exploiting the Web structured data for the health domain and presenting a system that allows different types of users, i.e., non-medical experts and medical experts, to retrieve Web pages with language complexity levels suitable to their expertise. Furthermore, we apply our methodology to the results of a generic search engine, such as Google, in order to re-rank them and provide different users with the proper health/medical Web pages in terms of language complexity

Metabolomic analyses of Leishmania reveal multiple species differences and large differences in amino acid metabolism

Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts

Periodontal parameters and cervical root resorption during orthodontic tooth movement

OBJECTIVES: To assess the relationship between periodontal parameters and cervical root resorption in orthodontically moved teeth. MATERIAL AND METHODS: In a standardized experimental tooth movement in 16 periodontally healthy subjects, 29 pre-molars were tipped buccally for 8 weeks. Eighteen contralateral pre-molars not subjected to orthodontic movement served as controls. Plaque Index (PI), Gingival Index (GI), probing depth and bleeding on probing were assessed three times before and six times during the experimental phase. Teeth were extracted and scanned in a micro-computed tomography scanner. The presence or absence, and the severity of cervical root resorption were evaluated on the three-dimensional reconstruction of the scans by two calibrated examiners. RESULTS: Overall, periodontal parameters were not different between the test and the control teeth. Clear signs of buccal cervical resorption were detected on 27 of 29 orthodontically moved teeth and on one control tooth. Ten subjects had perfect oral hygiene and no gingivitis, whereas six subjects showed a moderate level of plaque and gingivitis (>20% occurrences of PI or GI with >0). No relationship could be demonstrated between resorption and periodontal parameters. CONCLUSIONS: Nearly all orthodontically moved teeth showed signs of cervical resorption. Periodontal parameters were unrelated to this important side effect of orthodontic treatment