Photon extrabunching in ultrabright twin beams measured by two-photon counting in a semiconductor

For many years twin beams originating from parametric down-converted light beams have aroused great interest and attention in the photonics community. One particular aspect of the twin beams is their peculiar intensity correlation functions, which are related to the coincidence rate of photon pairs. Here we take advantage of the huge bandwidth offered by two-photon absorption in a semiconductor to quantitatively determine correlation functions of twin beams generated by spontaneous parametric down-conversion. Compared with classical incoherent sources, photon extrabunching is unambiguously and precisely measured, originating from exact coincidence between down-converted pairs of photons, travelling in unison. These results strongly establish that two-photon counting in semiconductors is a powerful tool for the absolute measurement of light beam photon correlations at ultrashort timescales

Noninvasive Monitoring of Placenta-Specific Transgene Expression by Bioluminescence Imaging

BACKGROUND: Placental dysfunction underlies numerous complications of pregnancy. A major obstacle to understanding the roles of potential mediators of placental pathology has been the absence of suitable methods for tissue-specific gene manipulation and sensitive assays for studying gene functions in the placentas of intact animals. We describe a sensitive and noninvasive method of repetitively tracking placenta-specific gene expression throughout pregnancy using lentivirus-mediated transduction of optical reporter genes in mouse blastocysts. METHODOLOGY/PRINCIPAL FINDINGS: Zona-free blastocysts were incubated with lentivirus expressing firefly luciferase (Fluc) and Tomato fluorescent fusion protein for trophectoderm-specific infection and transplanted into day 3 pseudopregnant recipients (GD3). Animals were examined for Fluc expression by live bioluminescence imaging (BLI) at different points during pregnancy, and the placentas were examined for tomato expression in different cell types on GD18. In another set of experiments, blastocysts with maximum photon fluxes in the range of 2.0E+4 to 6.0E+4 p/s/cm(2)/sr were transferred. Fluc expression was detectable in all surrogate dams by day 5 of pregnancy by live imaging, and the signal increased dramatically thereafter each day until GD12, reaching a peak at GD16 and maintaining that level through GD18. All of the placentas, but none of the fetuses, analyzed on GD18 by BLI showed different degrees of Fluc expression. However, only placentas of dams transferred with selected blastocysts showed uniform photon distribution with no significant variability of photon intensity among placentas of the same litter. Tomato expression in the placentas was limited to only trophoblast cell lineages. CONCLUSIONS/SIGNIFICANCE: These results, for the first time, demonstrate the feasibility of selecting lentivirally-transduced blastocysts for uniform gene expression in all placentas of the same litter and early detection and quantitative analysis of gene expression throughout pregnancy by live BLI. This method may be useful for a wide range of applications involving trophoblast-specific gene manipulations in utero

Central motor control failure in fibromyalgia: a surface electromyography study

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia (FM) is characterised by diffuse musculoskeletal pain and stiffness at multiple sites, tender points in characteristic locations, and the frequent presence of symptoms such as fatigue. The aim of this study was to assess whether the myoelectrical manifestations of fatigue in patients affected by FM are central or peripheral in origin.</p> <p>Methods</p> <p>Eight female patients aged 55.6 ± 13.6 years (FM group) and eight healthy female volunteers aged 50.3 ± 9.3 years (MCG) were studied by means of non-invasive surface electromyography (s-EMG) involving a linear array of 16 electrodes placed on the skin overlying the biceps brachii muscle, with muscle fatigue being evoked by means of voluntary and involuntary (electrically elicited) contractions. Maximal voluntary contractions (MVCs), motor unit action potential conduction velocity distributions (mean ± SD and skewness), and the mean power frequency of the spectrum (MNF) were estimated in order to assess whether there were any significant differences between the two groups and contraction types.</p> <p>Results</p> <p>The motor pattern of recruitment during voluntary contractions was altered in the FM patients, who also showed fewer myoelectrical manifestations of fatigue (normalised conduction velocity rate of changes: -0.074 ± 0.052%/s in FM vs -0.196 ± 0.133%/s in MCG; normalised MNF rate of changes: -0.29 ± 0.16%/s in FM vs -0.66 ± 0.34%/s in MCG). Mean conduction velocity distribution and skewnesses values were higher (p < 0.01) in the FM group. There were no between-group differences in the results obtained from the electrically elicited contractions.</p> <p>Conclusion</p> <p>The apparent paradox of fewer myoelectrical manifestations of fatigue in FM is the electrophysiological expression of muscle remodelling in terms of the prevalence of slow conducting fatigue-resistant type I fibres. As the only between-group differences concerned voluntary contractions, they are probably more related to central motor control failure than muscle membrane alterations, which suggests pathological muscle fibre remodelling related to altered suprasegmental control.</p

Effectiveness of an online group course for adolescents and young adults with depressive symptoms: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Depression is a common condition whose first onset is usually in late adolescence or early adulthood. Internet-based interventions are an effective treatment approach to depression. The aim of this study is to investigate the effectiveness of a Dutch online cognitive-behavioural group course known as Master Your Mood (<it>Grip op Je Dip</it>) for young people reporting depressive symptoms. Secondary research questions involve maintenance of effect at 6 months, mediators, and predictors of better outcomes.</p> <p>Methods</p> <p>We will conduct a randomised controlled trial (RCT) in which 244 young people aged 16-25 are randomly allocated to the Grip op Je Dip (GOJD) online group course or to a waiting list control group. The participants will be recruited from the general population. The primary outcome measure will be the severity of depressive symptoms according to the Center for Epidemiological Studies Depression Scale (CES-D). Other outcomes will include anxiety (Hospital Anxiety and Depression Scale-Anxiety, HADS) and mastery (Mastery Scale). Assessments will take place in both groups at baseline and three months later. Effect maintenance will be studied in the GOJD group six months after baseline, with missing data imputed using the expectation-maximisation method. Mediators and predictors of better outcomes will also be identified.</p> <p>Discussion</p> <p>The trial should add to the body of knowledge on the effectiveness of Internet-based interventions for depression. To our knowledge, this will be the first RCT on an online group intervention in this field.</p> <p>Trial registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=NTR1694">NTR1694</a></p

Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N–Terminal Peptide Binding

Ligand binding to certain classes of G protein coupled receptors (GPCRs) stimulates the rapid synthesis of cAMP through G protein. Human parathyroid hormone (PTH), a member of class B GPCRs, binds to its receptor via its N–terminal domain, thereby activating the pathway to this secondary messenger inside cells. Presently, GPCRs are the target of many pharmaceuticals however, these drugs target only a small fraction of structurally known GPCRs (about 10%). Coordination complexes are gaining interest due to their wide applications in the medicinal field. In the present studies we explored the potential of a coordination complex of Zn(II) and anthracenyl–terpyridine as a modulator of the parathyroid hormone response. Preferential interactions at the N–terminal domain of the peptide hormone were manifested by suppressed cAMP generation inside the cells. These observations contribute a regulatory component to the current GPCR–cAMP paradigm, where not the receptor itself, but the activating hormone is a target. To our knowledge, this is the first report about a coordination complex modulating GPCR activity at the level of deactivating its agonist. Developing such molecules might help in the control of pathogenic PTH function such as hyperparathyroidism, where control of excess hormonal activity is essentially required

Social context and sex moderate the association between type D personality and cardiovascular reactivity

peer-reviewedType D personality has been consistently associated with adverse cardiovascular health with atypical cardiovascular reactions to psychological stress one plausible underlying mechanism. However, whether this varies by sex and social context has received little attention. This study examined the interaction between Type D personality, sex and social context on cardiovascular reactivity to acute stress. A sample of 76 healthy undergraduate students (47 female) completed the DS14 Type D measure, before undergoing a traditional cardiovascular reactivity protocol. The social context of the laboratory environment was manipulated to create a social and non-social context using a between-subjects design. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were monitored throughout. No associations were evident for blood pressure. However, a significant personality × sex × social context interaction on HR reactivity was found; here Type D was associated with a higher HR response to the social task amongst males but not females, while Type D females typically exhibited blunted reactions. While these atypical reactions indicate a possible psychophysiological pathway leading to adverse cardiovascular events amongst Type Ds, it appears that Type D males are particularly vulnerable to socially based stressors, exhibiting exaggerated cardiovascular reactions.peer-reviewe

The importance of imprinting in the human placenta.

As a field of study, genomic imprinting has grown rapidly in the last 20 years, with a growing figure of around 100 imprinted genes known in the mouse and approximately 50 in the human. The imprinted expression of genes may be transient and highly tissue-specific, and there are potentially hundreds of other, as yet undiscovered, imprinted transcripts. The placenta is notable amongst mammalian organs for its high and prolific expression of imprinted genes. This review discusses the development of the human placenta and focuses on the function of imprinting in this organ. Imprinting is potentially a mechanism to balance parental resource allocation and it plays an important role in growth. The placenta, as the interface between mother and fetus, is central to prenatal growth control. The expression of genes subject to parental allelic expression bias has, over the years, been shown to be essential for the normal development and physiology of the placenta. In this review we also discuss the significance of genes that lack conservation of imprinting between mice and humans, genes whose imprinted expression is often placental-specific. Finally, we illustrate the importance of imprinting in the postnatal human in terms of several human imprinting disorders, with consideration of the brain as a key organ for imprinted gene expression after birth

At Least Ten Genes Define the Imprinted Dlk1-Dio3 Cluster on Mouse Chromosome 12qF1

Background: Genomic imprinting is an exception to Mendelian genetics in that imprinted genes are expressed monoallelically, dependent on parental origin. In mammals, imprinted genes are critical in numerous developmental and physiological processes. Aberrant imprinted gene expression is implicated in several diseases including Prader-Willi/ Angelman syndromes and cancer. Methodology/Principal Findings: To identify novel imprinted genes, transcription profiling was performed on two uniparentally derived cell lines, androgenetic and parthenogenetic primary mouse embryonic fibroblasts. A maternally expressed transcript termed Imprinted RNA near Meg3/Gtl2 (Irm) was identified and its expression studied by Northern blotting and whole mounts in situ hybridization. The imprinted region that contains Irm has a parent of origin effect in three mammalian species, including the sheep callipyge locus. In mice and humans, both maternal and paternal uniparental disomies (UPD) cause embryonic growth and musculoskeletal abnormalities, indicating that both alleles likely express essential genes. To catalog all imprinted genes in this chromosomal region, twenty-five mouse mRNAs in a 1.96Mb span were investigated for allele specific expression. Conclusions/Significance: Ten imprinted genes were elucidated. The imprinting of three paternally expressed protein coding genes (Dlk1, Peg11, and Dio3) was confirmed. Seven noncoding RNAs (Meg3/Gtl2, Anti-Peg11, Meg8, Irm/‘‘Rian’’