The neuropeptide gonadotropin-releasing hormone (GnRH) has a central role in the neural control of vertebrate reproduction. This review describes an overview of what is currently known about GnRH in ...vertebrates in the context of its structural and functional evolution. A large body of evidence has demonstrated the existence of three paralogous genes for GnRH (GnRH1, GnRH2 and GnRH3) in the vertebrate lineage. They are most probably the products of whole-genome duplications that occurred early in vertebrate evolution. Although GnRH3 has been identified only in teleosts, comparative genomic analyses indicated that GnRH3 has not arisen from a teleost-specific genome duplication, but has been derived from an earlier genome duplication in an ancestral vertebrate, followed by its loss in the tetrapod lineage. A loss of other paralogous genes has also occurred independently in different vertebrate lineages, leading to species-specific differences in the organization of the GnRH system. In addition to the GnRH3 gene, the GnRH2 gene has been deleted or silenced in certain mammalian species, while some teleosts seem to have lost the GnRH1 or GnRH3 gene. The duplicated GnRH genes have undergone subfunctionalization during the evolution of vertebrates; GnRH1 has become the major stimulator of gonadotropins and probably other pituitary hormones as well, whereas GnRH2 and GnRH3 would have functioned as neuromodulators, affecting reproductive behaviour. Conversely, in cases where a paralogous gene for GnRH has been lost, one of the remaining paralogues appears to have adopted its role.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Among gastrointestinal cancers, the prognosis of pancreatic cancer is one of the poorest, with a large number of patients being diagnosed with unresectable tumors at the first ...visit to a doctor. The aims of the present study were to investigate the circulating tumor cells (CTC) in peripheral blood in order to assess their clinical significance in patients with pancreatic cancer. Methods Sixty-five patients with advanced pancreatic cancer were enrolled. Borderline resectable pancreatic tumor patients were 9, and Unresectable patients were 56. The CellSearch system was used to isolate and enumerate CTCs. Results CTCs were identified in 21 out of 65 patients (32.3%) with only unresectable tumors. The overall survival rate was significantly lower in unresectable patients with than in those without CTCs ( P = 0.0051). CTC positivity was significantly higher in patients with than in those without liver metastasis. A multivariate analysis identified the presence or absence of CTCs as an independent prognostic factor. Follow-up blood specimens were obtained from 40 patients treated with chemotherapy or chemoradiotherapy. The incidences of CTC positivity at three months after beginning of treatments in patients with progressive disease and stable disease or a partial response were 45.4% and 24.1%, respectively. The overall survival rate was significantly lower in patients with than in those without CTCs even after treatments ( P = 0.045). Conclusion CTC numbers represents a useful tool for predicting prognoses and therapeutic responses to chemotherapy among patients with advanced pancreatic cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Nanocarbons, especially two-dimensional carbons, have received considerable attention due to their unique structure and physical and chemical properties, which make them promising candidate materials ...for biomedical applications. In this study, we focus on graphene oxide (GO), which has many oxygenated functional groups and high affinity with water and biomaterials, and the synthesis of GO complexes with antibacterial agents, like cetylpyridinium chloride (CPC) and its derivatives. We found that the sustained release of CPCs from GO can be controlled by changing the terminal functional group of CPC. The prepared GO-CPC complexes were subjected to antibacterial tests against S. mutans. CPC with the carboxy group was degraded by the oxidizing property of GO, resulting in the loss of antibacterial properties. On the other hand, the other CPC derivatives were released from GO and showed antibacterial activities. Finally, we propose a new mechanism describing how GO and CPC form a functional complex, and how CPC is released from this complex. These findings will lead to pioneering the carbon-based functional antibacterial agents designed at the molecular level.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Oxytocin, a mammalian neuropeptide primarily synthesised in the supraoptic and paraventricular nuclei of the hypothalamus, mediates a variety of physiological and behavioural processes, ranging from ...parturition and lactation to affiliation and prosociality. Multiple studies in rodents have shown that the expression of the oxytocin gene (Oxt) is stimulated by oestrogen, whereas androgen has no apparent effect. However, this finding is not consistent across all studies, and no study has examined sex steroid regulation of Oxt or its orthologues in other animals. In the present study, we show that, in the teleost fish, medaka (Oryzias latipes), the expression of the isotocin gene (it), the teleost orthologue of Oxt, in the parvocellular preoptic nuclei (homologous to the mammalian supraoptic nucleus) is male‐specifically up‐regulated by gonadal androgen, whereas it expression in the magnocellular/gigantocellular preoptic nuclei (homologous to the mammalian paraventricular nucleus) is independent of sex steroids in both sexes. None of the it‐expressing neurones appear to co‐express androgen receptors, suggesting that the effect of androgen on it expression is indirect. We found that the expression of a kisspeptin gene, kiss2, in the male brain is dependent on gonadal androgen, raising the possibility that the androgen‐dependent expression of it may be mediated by kiss2 neurones. Our data also show that the isotocin peptide synthesised in response to androgen is axonally transported to the posterior pituitary to act peripherally. Given that levels of it expression are higher in females than in males, androgen may serve to compensate for the female‐biased it expression to ensure a role for isotocin that is equally important for both sexes. These results are unexpectedly quite different from those reported in rodents, indicating that the regulatory role of sex steroids in Oxt/it expression has diverged during evolution, possibly with accompanying changes in the role of oxytocin/isotocin.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
We describe an approach to the high-fidelity measurement of a superconducting qubit using an on-chip microwave photon counter. The protocol relies on the transient response of a dispersively coupled ...measurement resonator to map the state of the qubit to “bright” and “dark” cavity pointer states that are characterized by a large differential photon occupation. Following this mapping, we photodetect the resonator using the Josephson photomultiplier, which transitions between classically distinguishable flux states when cavity photon occupation exceeds a certain threshold. Our technique provides access to the binary outcome of projective quantum measurement at the millikelvin stage without the need for quantum-limited preamplification and thresholding at room temperature. We achieve raw single-shot measurement fidelity in excess of 98% across multiple samples using this approach in total measurement times under 500 ns. In addition, we show that the backaction and crosstalk associated with our measurement protocol can be mitigated by exploiting the intrinsic damping of the Josephson photomultiplier itself.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM, UPUK
Highlights ► The medaka vasotocin is expressed only in males in two hypothalamic nuclei. ► The overall expression level of isotocin in medaka forebrain is higher in females. ► The medaka ...gonadotropin-releasing hormone 3 (GnRH3) shows a similar female bias. ► The medaka GnRH1 is expressed more abundantly in males in telencephalic nuclei. ► Tryptophan hydroxylases show male-biased expression in medaka telencephalon/thalamus.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A microfabricated directional coupler (DC) was used for the detection of DNA conjugated with quantum dots. Output optical signals from DCs of a wide range of device lengths correspond well to ...theoretical and simulation results. Even 20 µm-long DC devices could detect changes in the output optical intensity by monitoring the near-field pattern using a CCD camera. The signal was enhanced 60 × using a 1500 µm-long DC device. For large cladding refractive-index changes between air and water, the normalized signal changed cyclically several times between 0 and 1. The results suggest that the DC can be the basis for miniaturized two-dimensionally integrated biochemical sensors.
Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains ...like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second‐level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long‐term therapeutic strategy. Endotype‐driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The urocortin (UCN) group of neuropeptides includes urocortin 1/sauvagine/urotensin 1 (UTS1), urocortin 2 (UCN2) and urocortin 3 (UCN3). In recent years, evidence has accumulated showing that UCNs ...play pivotal roles in mediating stress response and anxiety in mammals. Evidence has also emerged regarding the evolutionary conservation of UCNs in vertebrates, but very little information is available about UCNs in non‐mammalian vertebrates. Indeed, at present, there are no reports of the empirical identification of ucn2 in non‐mammalian vertebrates or of the distribution of ucn2 and ucn3 expression in the adult central nervous system (CNS) of these animals. To gain insight into the evolutionary nature of UCNs in vertebrates, we cloned uts1, ucn2 and ucn3 in a teleost fish, medaka and examined the spatial expression of these genes in the adult brain and spinal cord. Although all known UCN2 genes except those in rodents have been reported to likely lack the necessary structural features to produce a functional pre‐pro‐protein, all three UCN genes in medaka, including ucn2, displayed all of these features, suggesting their functionality. The three UCN genes exhibited distinct spatial expression patterns in the medaka brain: uts1 was primarily expressed in broad regions of the dorsal telencephalon, ucn2 was expressed in restricted regions of the thalamus and brainstem and ucn3 was expressed in discrete nuclei throughout many regions of the brain. We also found that these genes were all expressed throughout the medaka spinal cord, each with a distinct spatial pattern. Given that many of these regions have been implicated in stress responses and anxiety, the three UCNs may serve distinct physiological roles in the medaka CNS, including those involved in stress and anxiety, as shown in the mammalian CNS.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
BodyParts3D is a dictionary-type database for anatomy in which anatomical concepts are represented by 3D structure data that specify corresponding segments of a 3D whole-body model for an adult human ...male. It encompasses morphological and geometrical knowledge in anatomy and complements ontological representation. Moreover, BodyParts3D introduces a universal coordinate system in human anatomy, which may facilitate management of samples and data in biomedical research and clinical practice. As of today, 382 anatomical concepts, sufficient for mapping materials in most molecular medicine experiments, have been specified. Expansion of the dictionary by adding further segments and details to the whole-body model will continue in collaboration with clinical researchers until sufficient resolution and accuracy for most clinical application are achieved. BodyParts3D is accessible at: http://lifesciencedb.jp/ag/bp3d/.
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