Daily rhythms of behavior are controlled by a circuit of circadian pacemaking neurons. In Drosophila, 150 pacemakers participate in this network, and recent observations suggest that the network is divisible into M and E oscillators, which normally interact and synchronize. Sixteen oscillator neurons (the small and large lateral neurons [LNvs]) express a neuropeptide called pigment-dispersing factor (PDF) whose signaling is often equated with M oscillator output. Given the significance of PDF signaling to numerous aspects of behavioral and molecular rhythms, determining precisely where and how signaling via the PDF receptor (PDFR) occurs is now a central question in the field. Here we show that GAL4-mediated rescue of pdfr phenotypes using a UAS-PDFR transgene is insufficient to provide complete behavioral rescue. In contrast, we describe a approximately 70-kB PDF receptor (pdfr) transgene that does rescue the entire pdfr circadian behavioral phenotype. The transgene is widely but heterogeneously expressed among pacemakers, and also among a limited number of non-pacemakers. Our results support an important hypothesis: the small LNv cells directly target a subset of the other crucial pacemaker neurons cells. Furthermore, expression of the transgene confirms an autocrine feedback signaling by PDF back to PDF-expressing cells. Finally, the results present an unexpected PDF receptor site: the large LNv cells appear to target a population of non-neuronal cells that resides at the base of the eye.

BACKGROUND

Syphilis remains a major public health problem in Europe (both in Eastern Europe since the 1990's and in Western Europe since the re-emergence of the disease in the late 1990's-early 2000's).

METHODS

This guideline is an update of the IUSTI: 2008 European guideline on the management of syphilis and is produced by the European Guideline Editorial Board (http://www.iusti.org/regions/Europe/pdf/2013/Editorial_Board.pdf) and EDF Guideline Committee.

RESULTS

It provides recommendations concerning the diagnosis and management of syphilis in Europe. Major advances include (1) broader use of PCR, immunohistochemistry, subtyping of the etiological agent Treponema pallidum subspecies pallidum, new treponemal tests, and rapid-point-of-care (POC) tests detecting both treponemal and non-treponemal antibodies, (2) more flexible options for screening (TT-treponemal test- first or NTT -non treponemal test- first or both TT and NTT), and (3) procaine penicillin is no longer the first line therapy option in any phase of the disease, i.e. long acting penicillin G (i.e. benzathine penicillin G-BPG) is the only first line therapy regimen in early syphilis and in late latent syphilis.

CONCLUSIONS

Syphilis is a disease that is relatively easy to detect by appropriate serological tests, however, all laboratory results should be considered together with clinical data and sexual risk anamnesis. Syphilis is also easy to treat with BPG. A major concern about the supply of BPG in many European countries could threaten the efficacy of the policies of eradication of the disease in Europe.

Clock output pathways are central to convey timing information from the circadian clock to a diversity of physiological systems, ranging from cell-autonomous processes to behavior. While the molecular mechanisms that generate and sustain rhythmicity at the cellular level are well understood, it is unclear how this information is further structured to control specific behavioral outputs. Rhythmic release of pigment dispersing factor (PDF) has been proposed to propagate the time of day information from core pacemaker cells to downstream targets underlying rhythmic locomotor activity. Indeed, such circadian changes in PDF intensity represent the only known mechanism through which the PDF circuit could communicate with its output. Here we describe a novel circadian phenomenon involving extensive remodeling in the axonal terminals of the PDF circuit, which display higher complexity during the day and significantly lower complexity at nighttime, both under daily cycles and constant conditions. In support to its circadian nature, cycling is lost in bona fide clockless mutants. We propose this clock-controlled structural plasticity as a candidate mechanism contributing to the transmission of the information downstream of pacemaker cells.

About 150 clock neurons are clustered in different groups in the brain of Drosophila. Among these clock neurons, some pigment-dispersing factor (PDF)-positive and PDF-negative lateral neurons (LNs) are principal oscillators responsible for bouts of activity in the morning and evening, respectively. The full complement of neurotransmitters in these morning and evening oscillators is not known. By using a screen for candidate neuromediators in clock neurons, we discovered ion transport peptide (ITP) and short neuropeptide F (sNPF) as novel neuropeptides in subpopulations of dorsal (LN(d)s) and ventral (s-LN(v)s) LNs. Among the six LN(d)s, ITP was found in one that coexpresses long neuropeptide F (NPF) and cryptochrome. We detected sNPF in two LN(d)s that also express cryptochrome; these cells are distinct from three LN(d)s expressing NPF. Thus, we have identified neuropeptides in five of the six LN(d)s. The three LN(d)s expressing cryptochrome, with either ITP or sNPF, are the only ones with additional projections to the accessory medulla. Among the five s-LN(v)s in the adult brain, ITP was detected in the fifth neuron that is devoid of PDF and sNPF in the four neurons that also express PDF. By using a choline acetyltransferase (Cha) Gal4, we detected Cha expression in the two sNPF producing LN(d)s and in the fifth s-LN(v). In the larval brain, two of the four PDF-producing s-LN(v)s coexpress sNPF. Our findings emphasize that the LN(d)s are heterogeneous both anatomically and with respect to content of neuropeptides, cryptochrome, and other markers and suggest diverse functions of these neurons.

The underlying molecular pathogenic mechanisms remain unknown in the majority of human pituitary tumors. GADD45 gamma is a member of a growth arrest and DNA damage-inducible gene family that functions in the negative regulation of cell growth. We have found that the mRNA expression of the GADD45 gamma gene is significantly different between normal human pituitary tissue and clinically nonfunctioning pituitary adenomas using cDNA-representational difference analysis. Although GADD45 gamma mRNA was found in normal human pituitary tissue, it was detectable in only 1 of 18 clinically nonfunctioning pituitary tumors by RT-PCR. Furthermore, this gene was not expressed in the majority of GH- or PRL-secreting pituitary tumors (6 of 8 and 7 of 10, respectively). In colony formation assays, transfection of human GADD45 gamma cDNA into the human pituitary tumor-derived cell line, PDFS, results in a dramatic decrease in cell growth by 88%. GADD45 gamma also reduces colony formation in other pituitary tumor-derived cell lines, AtT20 and GH4, by approximately 60% and 50%, respectively, confirming its function in controlling cell proliferation in the pituitary. These data indicate that GADD45 gamma is a powerful growth suppressor controlling pituitary cell proliferation, and GADD45 gamma represents the first identified gene whose expression is lost in the majority of human pituitary tumors.

Our recent studies on rat pituitary tissue suggest that the annexin 1 (ANXA1)-dependent inhibitory actions of glucocorticoids on ACTH secretion are effected via a paracrine mechanism that involves protein kinase C (PKC)-dependent translocation of a serine-phosphorylated species of ANXA1 (Ser-P-ANXA1) to the plasma membrane of the nonsecretory folliculostellate cells. In the present study, we have used a human folliculostellate cell line (PDFS) to explore the signaling mechanisms that cause the translocation of Ser-P-ANXA1 to the membrane together with Western blot analysis and flow cytometry to detect the phosphorylated protein. Exposure of PDFS cells to dexamethasone caused time-dependent increases in the expression of ANXA1 mRNA and protein, which were first detected within 2 h of steroid contact. This genomic response was preceded by the appearance within 30 min of substantially increased amounts of Ser-P-ANXA1 and by translocation of the phosphorylated protein to the cell surface. The prompt membrane translocation of Ser-P-ANXA1 provoked by dexamethasone was inhibited by the glucocorticoid receptor, antagonist, mifepristone, but not by actinomycin D or cycloheximide, which effectively inhibit mRNA and protein synthesis respectively in our preparation. It was also inhibited by a nonselective PKC inhibitor (PKC(9-31)), by a selective inhibitor of Ca(2+)-dependent PKCs (Go 6976) and by annexin 5 (which sequesters PKC in other systems). In addition, blockade of phosphatidylinositiol 3-kinase (wortmannin) or MAPK pathways with PD 98059 or UO 126 (selective for MAPK kinse 1 and 2) prevented the steroid-induced translocation of Ser-P-ANXA1 to the cell surface. These results suggest that glucocorticoids induce rapid serine phosphorylation and membrane translocation of ANXA1 via a novel nongenomic, glucocorticoid receptor-dependent mechanism that requires MAPK, phosphatidylinositiol 3-kinase, and Ca(2+)-dependent PKC pathways.

The MAL6 locus is one of five closely related unlinked loci, any one of which is sufficient for fermentation of maltose in Saccharomyces. Previous genetic analysis indicated that this locus is defined by two complementation groups, MALp and MALg. MALp reportedly is a regulatory gene required for inducible synthesis of the two enzymatic functions needed for fermentation: maltose permease and maltase. We have investigated the physical and genetic structure of the MAL6 locus, which has been isolated on a recombinant DNA plasmid. One subclone of the region, pDF-1, was found to encode a single transcribed region and to contain the MALp gene. A second subclone, p1, was shown to contain the MALg function but surprisingly had not one but two maltose-inducible transcripts. Subclones having only one of these transcribed regions lacked MALg activity. The three transcribed regions have been named MAL61 and MAL62, which correspond to MALg, and MAL63, which corresponds to MALp. This clustered arrangement of a regulatory gene adjacent to the sequences it controls has not previously been described in eukaryotes and is reminiscent of bacterial operons except that the messenger RNA molecules are not polycistronic.

The question of whether influenza is transmitted to a significant degree by aerosols remains controversial, in part, because little is known about the quantity and size of potentially infectious airborne particles produced by people with influenza. In this study, the size and amount of aerosol particles produced by nine subjects during coughing were measured while they had influenza and after they had recovered, using a laser aerosol particle spectrometer with a size range of 0.35 to 10 μm. Individuals with influenza produce a significantly greater volume of aerosol when ill compared with afterward (p = 0.0143). When the patients had influenza, their average cough aerosol volume was 38.3 picoliters (pL) of particles per cough (SD 43.7); after patients recovered, the average volume was 26.4 pL per cough (SD 45.6). The number of particles produced per cough was also higher when subjects had influenza (average 75,400 particles/cough, SD 97,300) compared with afterward (average 52,200, SD 98,600), although the difference did not reach statistical significance (p = 0.1042). The average number of particles expelled per cough varied widely from patient to patient, ranging from 900 to 302,200 particles/cough while subjects had influenza and 1100 to 308,600 particles/cough after recovery. When the subjects had influenza, an average of 63% of each subject's cough aerosol particle volume in the detection range was in the respirable size fraction (SD 22%), indicating that these particles could reach the alveolar region of the lungs if inhaled by another person. This enhancement in aerosol generation during illness may play an important role in influenza transmission and suggests that a better understanding of this phenomenon is needed to predict the production and dissemination of influenza-laden aerosols by people infected with this virus. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a PDF file of demographic information, influenza test results, and volume and peak flow rate during each cough and a PDF file containing number and size of aerosol particles produced.].

By using both numerical and analytical approaches, we have shown that heterosis alone is not a mechanism for maintaining many alleles segregating at a locus. Even when all heterozygous are more fit than all homozygotes, the proportion of fitness arrays that will lead to a stable, feasible equilibrium of more than 6 or 7 alleles is vanishingly small. More alleles can be maintained if, in addition to heterosis, it is assumed that there is very little variation in fitness from heterozygote to heterozygote, with the ratio of mean heterosis to standard deviation of fitness among heterozygotes in the neighborhood of 10. When such conditions hold, the allelic frequency distribution and equilibrium will be very uniform, with all alleles very close to equal frequency (see PDF). It is much more likely that stable equilibria for multiple alleles will be best explained by multiple niche selection.

In order to assess the functional roles of heat stress-induced class B-heat shock factors in Arabidopsis, we investigated T-DNA knockout mutants of AtHsfB1 and AtHsfB2b. Micorarray analysis of double knockout hsfB1/hsfB2b plants revealed as strong an up-regulation of the basal mRNA-levels of the defensin genes PdfPdf expression was further enhanced by jasmonic acid treatment or infection with the necrotrophic fungus Alternaria brassicicola. The single mutant hsfB2b and the double mutant hsfB1/B2b were significantly improved in disease resistance after A. brassicicola infection. There was no indication for a direct interaction of Hsf with the promoter of PdfPdf genes as targets of Hsf-dependent negative regulation is the first evidence for an interconnection of Hsf in the regulation of biotic and abiotic responses.

OBJECTIVE

To confirm the prognostic value of a drug resistance profile combining prednisolone, vincristine, and l-asparaginase (PVA) cytotoxicity in an independent group of children with acute lymphoblastic leukemia (ALL) treated with a different protocol and analyzed at longer follow-up compared with our previous study of patients treated according to the Dutch Childhood Leukemia Study Group (DCLSG) ALL VII/VIII protocol.

METHODS

Drug resistance profiles were determined in 202 children (aged 1 to 18 years) with newly diagnosed ALL who were treated according to the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)-92 protocol.

RESULTS

At a median follow-up of 6.2 years (range, 4.1 to 9.3 years), the 5-year disease-free survival probability (<em>pDFS</em>) rate +/- SE was 69% +/- 7.0%, 83% +/- 4.4%, and 84% +/- 6.8% for patients with resistant (PVA score 7 to 9), intermediate-sensitive (PVA score 5 to 6), and sensitive (SPVA score 3 to 4) profiles, respectively (sensitive and intermediate-sensitive v resistant, P </=.05). Resistant patients were at increased risk of an early event (nonresponse or relapse within 2.5 years of diagnosis) compared with sensitive and intermediate-sensitive patients (P =.03). The profile did not identify patients at higher risk of late relapse, which was also observed for DCLSG ALL-VII/VIII patients now analyzed at a median of 7.5 years of follow-up (range, 4.4 to 10.8 years). Despite being nondiscriminative for late relapses, the resistant profile was still the strongest prognostic factor for COALL-92 patients in a multivariate analysis including known risk factors (P =.07).

CONCLUSIONS

Drug resistance profiles identify patients at higher risk of early treatment failures and may, therefore, be used to improve risk-group stratification of children with ALL.

OBJECTIVE

Neuroendocrine-immune models have been proposed to account for the frequent co-occurrence of pain, depression, and fatigue (PDF) among cancer patients.

METHODS

In a cross-sectional observational study of advanced cancer patients (N = 104), we tested the hypothesis that the PDF cluster covaries with proposed biological mediators: hormones of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis.

METHODS

PDF symptoms were measured using the Brief Pain Inventory, Fatigue Symptom Inventory, and the Center for Epidemiological Studies Depression scales. HPA activation was indicated by plasma levels of cortisol and adrenocorticotropic hormone, and SNS activation was indicated by plasma epinephrine and norepinephrine.

RESULTS

Preliminary analyses supported the use of covariance structure modeling to test whether shared variance among hormone levels predicted shared variance among PDF symptoms. Latent variable analysis indicated that neuroendocrine levels predicted PDF (standardized beta = .23, p = .039), while controlling for important disease and demographic variables.

CONCLUSIONS

Previous studies have linked individual symptoms to individual biomarkers. The observed significant paring of the 4 hormones to the PDF cluster provides the first evidence suggestive of stress hormones as a common mechanism for the co-occurrence of pain, depression, and fatigue symptoms.

We present LO, NLO and NNLO sets of parton distribution functions (<em>PDFs</em>) of the proton determined from global analyses of the available hard scattering data. These MMHT2014 <em>PDFs</em> supersede the 'MSTW2008' parton sets, but they are obtained within the same basic framework. We include a variety of new data sets, from the LHC, updated Tevatron data and the HERA combined H1 and ZEUS data on the total and charm structure functions. We also improve the theoretical framework of the previous analysis. These new <em>PDFs</em> are compared to the 'MSTW2008' parton sets. In most cases the <em>PDFs</em>, and the predictions, are within one standard deviation of those of MSTW2008. The major changes are the [Formula: see text] valence quark difference at small [Formula: see text] due to an improved parameterisation and, to a lesser extent, the strange quark <em>PDF</em> due to the effect of certain LHC data and a better treatment of the [Formula: see text] branching ratio. We compare our MMHT <em>PDF</em> sets with those of other collaborations; in particular with the NN<em>PDF</em>3.0 sets, which are contemporary with the present analysis.

Rett syndrome (RTT) is a neurodevelopmental disorder affecting primarily females, with an incidence of around 1 in 15,000 females. In 1999, mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2) were first reported in RTT subjects, and since that time there have been a number of publications describing cohorts of patients and their mutations. In addition, MECP2 mutations have been reported in patients who do not fit the diagnostic criteria for Rett syndrome. We have developed a new locus-specific database, RettBASE (http://mecp2.chw.edu.au/), loosely based on the PAHdb website. The aim is to obtain data relating to all known instances of MECP2 variations, including published ta and data directly submitted by one of various means (either by using an online submission form, or by sending the same form in Adobe portable document format (pdf) or Microsoft Word format by email or fax to the database curators). The database has a range of query capabilities, allowing for simple or complex interrogation of the database. To address the issue of patient confidentiality, we have incorporated an Excel spreadsheet algorithm that allows the generation of a unique number based on the subject's name and date of birth. We believe this database will prove to be a useful resource, allowing the development of accurate prevalence data for disease-causing mutations, providing a catalog of polymorphisms, and potentially allowing more accurate phenotype-genotype correlations to be drawn.

Drosophila melanogaster display overt circadian rhythms in rest:activity behavior and eclosion. These rhythms have an endogenous period of approximately 24 hr and can adjust or "entrain" to environmental inputs such as light. Circadian rhythms depend upon a functioning molecular clock that includes the core clock genes period and timeless (reviewed in and ). Although we know that a clock in the lateral neurons (LNs) of the brain controls rest:activity rhythms, the cellular basis of eclosion rhythms is less well understood. We show that the LN clock is insufficient to drive eclosion rhythms. We establish that the prothoracic gland (PG), a tissue required for fly development, contains a functional clock at the time of eclosion. This clock is required for normal eclosion rhythms. However, both the PG clock function and eclosion rhythms require the presence of LNs. In addition, we demonstrate that pigment-dispersing factor (PDF), a neuropeptide secreted from LNs, is necessary for the PG clock and eclosion rhythms. Unlike other clocks in the fly periphery, the PG is similar to mammalian peripheral oscillators because it depends upon input, including PDF, from central pacemaker cells. This is the first report of a peripheral clock necessary for a circadian event.

Recently, colonic health has been linked to the maintaining overall health status and reducing the risk of diseases by changes in lifestyle. Functional foods, such as "prebiotics" and "probiotics", dietary fibers, and other dietary components that target the colon and affect its environment enhancing short fatty acid (SCFA) production have been at the forefront. The topic of this review is the key end products of colonic fermentation, the SCFA butyric, acetic, and propionic acids. SCFA are readily absorbed. Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues. Specific SCFA may reduce the risk of developing gastrointestinal disorders, cancer, and cardiovascular disesase (Fig. 1, Ref. 30). Full Text (Free, PDF) www.bmj.sk.

A fundamental property of circadian rhythms is their ability to persist under constant conditions. In Drosophila, the ventral Lateral Neurons (LNvs) are the pacemaker neurons driving circadian behavior under constant darkness. Wild-type flies are arrhythmic under constant illumination, but flies defective for the circadian photoreceptor CRY remain rhythmic. We found that flies overexpressing the pacemaker gene per or the morgue gene are also behaviorally rhythmic under constant light. Unexpectedly, the LNvs do not drive these rhythms: they are molecularly arrhythmic, and PDF--the neuropeptide they secrete to synchronize behavioral rhythms under constant darkness--is dispensable for rhythmicity in constant light. Molecular circadian rhythms are only found in a group of Dorsal Neurons: the DN1s. Thus, a subset of Dorsal Neurons shares with the LNvs the ability to function as pacemakers for circadian behavior, and its importance is promoted by light.

A method is presented for extracting the configurational entropy of solute molecules from molecular dynamics simulations, in which the entropy is computed as an expansion of multidimensional mutual information terms, which account for correlated motions among the various internal degrees of freedom of the molecule. The mutual information expansion is demonstrated to be equivalent to estimating the full-dimensional configurational probability density function (PDF) using the generalized Kirkwood superposition approximation (GKSA). While the mutual information expansion is derived to the full dimensionality of the molecule, the current application uses a truncated form of the expansion in which all fourth- and higher-order mutual information terms are neglected. Truncation of the mutual information expansion at the nth order is shown to be equivalent to approximating the full-dimensional PDF using joint PDFs with dimensionality of n or smaller by successive application of the GKSA. The expansion method is used to compute the absolute (classical) configurational entropy in a basis of bond-angle-torsion internal coordinates for several small molecules as well as the change in entropy upon binding for a small host-guest system. Convergence properties of the computed entropy values as a function of simulation time are investigated and comparisons are made with entropy values from the second generation Mining Minima software. These comparisons demonstrate a deviation in -TS of no more than about 2 kcal/mol for all cases in which convergence has been obtained.

The ventral lateral neurons (LNvs) of the Drosophila brain that express the period (per) and pigment dispersing factor (pdf) genes play a major role in the control of circadian activity rhythms. A new P-gal4 enhancer trap line is described that is mostly expressed in the LNvs This P-gal4 line was used to ablate the LNvs by using the pro-apoptosis gene bax, to stop PER protein oscillations by overexpressing per and to block synaptic transmission with the tetanus toxin light chain (TeTxLC). Genetic ablation of these clock cells leads to the loss of robust 24-h activity rhythms and reveals a phase advance in light-dark conditions as well as a weak short-period rhythm in constant darkness. This behavioural phenotype is similar to that described for disconnected1 (disco1) mutants, in which we show that the majority of the individuals have a reduced number of dorsally projecting lateral neurons which, however, fail to express PER. In both LNv-ablated and disco1 flies, PER cycles in the so-called dorsal neurons (DNs) of the superior protocerebrum, suggesting that the weak short-period rhythm could stem from these PDF-negative cells. The overexpression of per in LNs suppresses PER protein oscillations and leads to the disruption of both activity and eclosion rhythms, indicating that PER cycling in these cells is required for both of these rhythmic behaviours. Interestingly, flies overexpressing PER in the LNs do not show any weak short-period rhythms, although PER cycles in at least a fraction of the DNs, suggesting a dominant role of the LNs on the behavioural rhythms. Expression of TeTxLC in the LNvs does not impair activity rhythms, which indicates that the PDF-expressing neurons do not use synaptobrevin-dependent transmission to control these rhythms.

Animal circadian clocks are based on multiple oscillators whose interactions allow the daily control of complex behaviors. The Drosophila brain contains a circadian clock that controls rest-activity rhythms and relies upon different groups of PERIOD (PER)-expressing neurons. Two distinct oscillators have been functionally characterized under light-dark cycles. Lateral neurons (LNs) that express the pigment-dispersing factor (PDF) drive morning activity, whereas PDF-negative LNs are required for the evening activity. In constant darkness, several lines of evidence indicate that the LN morning oscillator (LN-MO) drives the activity rhythms, whereas the LN evening oscillator (LN-EO) does not. Since mutants devoid of functional CRYPTOCHROME (CRY), as opposed to wild-type flies, are rhythmic in constant light, we analyzed transgenic flies expressing PER or CRY in the LN-MO or LN-EO. We show that, under constant light conditions and reduced CRY function, the LN evening oscillator drives robust activity rhythms, whereas the LN morning oscillator does not. Remarkably, light acts by inhibiting the LN-MO behavioral output and activating the LN-EO behavioral output. Finally, we show that PDF signaling is not required for robust activity rhythms in constant light as opposed to its requirement in constant darkness, further supporting the minor contribution of the morning cells to the behavior in the presence of light. We therefore propose that day-night cycles alternatively activate behavioral outputs of the Drosophila evening and morning lateral neurons.

BACKGROUND

In Arabidopsis thaliana (L.) Heynh and Oryza sativa L., a large number of genes encode proteins of unknown functions, whose characterization still remains one of the major challenges. With an aim to characterize these unknown proteins having defined features (PDFs) in plants, we have chosen to work on proteins having a cystathionine beta-synthase (CBS) domain. CBS domain as such has no defined function(s) but plays a regulatory role for many enzymes and thus helps in maintaining the intracellular redox balance. Its function as sensor of cellular energy has also been widely suggested.

RESULTS

Our analysis has identified 34 CBS domain containing proteins (CDCPs) in Arabidopsis and 59 in Oryza. In most of these proteins, CBS domain coexists with other functional domain(s), which may indicate towards their probable functions. In order to investigate the role(s) of these CDCPs, we have carried out their detailed analysis in whole genomes of Arabidopsis and Oryza, including their classification, nomenclature, sequence analysis, domain analysis, chromosomal locations, phylogenetic relationships and their expression patterns using public databases (MPSS database and microarray data). We have found that the transcript levels of some members of this family are altered in response to various stresses such as salinity, drought, cold, high temperature, UV, wounding and genotoxic stress, in both root and shoot tissues. This data would be helpful in exploring the so far obscure functions of CBS domain and CBS domain-containing proteins in plant stress responses.

CONCLUSIONS

We have identified, classified and suggested the nomenclature of CDCPs in Arabidopsis and Oryza. A comprehensive analysis of expression patterns for CDCPs using the already existing transcriptome profiles and MPSS database reveals that a few CDCPs may have an important role in stress response/tolerance and development in plants, which needs to be validated further through functional genomics.

Orthodontic tooth movement is achieved by (re)modeling processes of the alveolar bone, which are triggered by changes in the stress/strain distribution in the periodontium. In the past, the finite element (FE) method has been used to describe the stressed situation within the periodontal ligament (PDL) and surrounding alveolar bone. The present study sought to determine the impact of the modeling process on the outcome from FE analyses and to relate these findings to the current theories on orthodontic tooth movement. In a series of FE analyses simulating teeth subjected to orthodontic loading, the influence of geometry/morphology, material properties, and boundary conditions was evaluated. The accurate description of alveolar bone morphology and the assignment of non-linear mechanical properties for the PDF elements demonstrate that loading of the periodontium cannot be explained in simple terms of compression and tension along the loading direction. Tension in the alveolar bone was far more predominant than compression.

In Drosophila, the amidated neuropeptide pigment dispersing factor (PDF) is expressed by the ventral subset of lateral pacemaker neurons and is required for circadian locomotor rhythms. Residual rhythmicity in pdf mutants likely reflects the activity of other neurotransmitters. We asked whether other neuropeptides contribute to such auxiliary mechanisms. We used the gal4/UAS system to create mosaics for the neuropeptide amidating enzyme PHM; amidation is a highly specific and widespread modification of secretory peptides in Drosophila. Three different gal4 drivers restricted PHM expression to different numbers of peptidergic neurons. These mosaics displayed aberrant locomotor rhythms to degrees that paralleled the apparent complexity of the spatial patterns. Certain PHM mosaics were less rhythmic than pdf mutants and as severe as per mutants. Additional gal4 elements were added to the weakly rhythmic PHM mosaics. Although adding pdf-gal4 provided only partial improvement, adding the widely expressed tim-gal4 largely restored rhythmicity. These results indicate that, in Drosophila, peptide amidation is required for neuropeptide regulation of behavior. They also support the hypothesis that multiple amidated neuropeptides, acting upstream, downstream, or in parallel to PDF, help organize daily locomotor rhythms.

To study the function of the neuropeptide pigment-dispersing factor (PDF) in the circadian system of Drosophila, we misexpressed the pdf gene from the grasshopper Romalea in the CNS of Drosophila and investigated the effect of this on behavioral rhythmicity. pdf was either ectopically expressed in different numbers of neurons in the brain or the thoracical nervous system or overexpressed in the pacemaker neurons alone. We found severe alterations in the activity and eclosion rhythm of several but not all lines with ectopic pdf expression. Only ectopic pdf expression in neurons that projected into the dorsal central brain severely influenced activity rhythms. Therefore, we conclude that PDF acts as a neuromodulator in the dorsal central brain that is involved in the rhythmic control of behavior. Overexpression of pdf in the pacemaker neurons alone or in the other neurons that express the clock genes period (per) and timeless (tim) did not disturb the activity rhythm. Such flies still showed a rhythm in PDF accumulation in the central brain terminals. This rhythm was absent in the terminals of neurons that expressed PDF ectopically. Probably, PDF is rhythmically processed, transported, or secreted in neurons expressing per and tim, and additional PDF expression in these cells does not influence this rhythmic process. In neurons lacking per and tim, PDF appears to be continuously processed, leading to a constant PDF secretion at their nerve terminals. This may lead to conflicting signals in the rhythmic output pathway and result in a severely altered rhythmic behavior.