Neurokinin 3 receptor antagonists compared with serotonin norepinephrine reuptake inhibitors for non-hormonal treatment of menopausal hot flushes : a systematic qualitative review

Hot flushes/flashes (HFs) or other vasomotor symptoms affect between 45 and 97% of women during menopause. Hormone replacement therapy (HRT) is effective at alleviating menopausal symptoms, but some women cannot or prefer not to take HRT. Since current non-hormonal options have suboptimal efficacy/tolerability, there is a pressing need for an effective, well-tolerated alternative. The neurokinin 3 receptor (NK3R) has recently been implicated in the generation of menopausal HFs and represents a novel therapeutic target to ameliorate HF symptoms. This review aims to assess if NK3R antagonists (NK3Ras) are more effective than Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)—currently a common choice for non-hormonal treatment of menopausal HFs.Publisher PDFPeer reviewe

Light-sheet microscopy with attenuation-compensated propagation-invariant beams

Scattering and absorption limit the penetration of optical fields into tissue. We demonstrate a new approach for increased depth penetration in light-sheet microscopy: attenuation-compensation of the light field. This tailors an exponential intensity increase along the illuminating propagation-invariant field, enabling the redistribution of intensity strategically within a sample to maximize signal and minimize irradiation. A key attribute of this method is that only minimal knowledge of the specimen transmission properties is required. We numerically quantify the imaging capabilities of attenuation-compensated Airy and Bessel light sheets, showing that increased depth penetration is gained without compromising any other beam attributes. This powerful yet straightforward concept, combined with the self-healing properties of the propagation-invariant field, improves the contrast-to-noise ratio of light-sheet microscopy up to eightfold across the entire field of view in thick biological specimens. This improvement can significantly increase the imaging capabilities of light-sheet microscopy techniques using Airy, Bessel, and other propagation-invariant beam types, paving the way for widespread uptake by the biomedical community.</p

Generation of three-dimensional multiple spheroid model of olfactory ensheathing cells using floating liquid marbles

We describe a novel protocol for three-dimensional culturing of olfactory ensheathing cells (OECs), which can be used to understand how OECs interact with other cells in three dimensions. Transplantation of OECs is being trialled for repair of the paralysed spinal cord, with promising but variable results and thus the therapy needs improving. To date, studies of OEC behaviour in a multicellular environment have been hampered by the lack of suitable three-dimensional cell culture models. Here, we exploit the floating liquid marble, a liquid droplet coated with hydrophobic powder and placed on a liquid bath. The presence of the liquid bath increases the humidity and minimises the effect of evaporation. Floating liquid marbles allow the OECs to freely associate and interact to produce OEC spheroids with uniform shapes and sizes. In contrast, a sessile liquid marble on a solid surface suffers from evaporation and the cells aggregate with irregular shapes. We used floating liquid marbles to co-culture OECs with Schwann cells and astrocytes which formed natural structures without the confines of gels or bounding layers. This protocol can be used to determine how OECs and other cell types associate and interact while forming complex cell structuresJSJ was funded by a grant from the Perry Cross Spinal Research Foundation; NTN was funded from Griffith University through a start-up grant and a grant from the Griffith University Research Infrastructure Program; JAK was funded by an Australian Research Council Discovery Grant DP150104495; JT was funded by an Eskitis Institute scholarship; CO was funded by a Griffith Sciences scholarship; RV was funded by a Griffith University International Postgraduate Research Scholarshi

Making Forest Data Fair and Open

Los datos sobre los bosques tropicales tienen una gran demanda. Pero las mediciones forestales sobre el terreno son difíciles de sustentar y las personas que las realizan están en gran desventaja con respecto a los que las utilizan. Se propone un nuevo enfoque para datos forestales que se centre en las necesidades de los creadores de los datos y garantice que los usuarios y los financiadores contribuyan adecuadamente.Revisión por pares

The handedness-associated PCSK6 locus spans an intronic promoter regulating novel transcripts

We recently reported the association of the PCSK6 gene with handedness through a quantitative genome-wide association study (GWAS; P < 0.5 × 10(-8)) for a relative hand skill measure in individuals with dyslexia. PCSK6 activates Nodal, a morphogen involved in regulating left-right body axis determination. Therefore, the GWAS data suggest that the biology underlying the patterning of structural asymmetries may also contribute to behavioural laterality, e.g. handedness. The association is further supported by an independent study reporting a variable number tandem repeat (VNTR) within the same PCSK6 locus to be associated with degree of handedness in a general population cohort. Here, we have conducted a functional analysis of the PCSK6 locus combining further genetic analysis, in silico predictions and molecular assays. We have shown that the previous GWAS signal was not tagging a VNTR effect, suggesting that the two markers have independent effects. We demonstrated experimentally that one of the top GWAS-associated markers, rs11855145, directly alters the binding site for a nuclear factor. Furthermore, we have shown that the predicted regulatory region adjacent to rs11855415 acts as a bidirectional promoter controlling the expression of novel RNA transcripts. These include both an antisense long non-coding RNA (lncRNA) and a short PCSK6 isoform predicted to be coding. This is the first molecular characterization of a handedness-associated locus that supports the role of common variants in non-coding sequences in influencing complex phenotypes through gene expression regulation

A decade of GRB follow-up by BOOTES in Spain (2003-2013)

This article covers ten years of GRB follow-ups by the Spanish BOOTES stations: 71 follow-ups providing 23 detections. Follow-ups by BOOTES-1B from 2005 to 2008 were given in the previous article, and are here reviewed, updated, and include additional detection data points as the former article merely stated their existence. The all-sky cameras CASSANDRA have not yet detected any GRB optical afterglows, but limits are reported where available

Photostimulation for in vitro optogenetics with high power blue organic light-emitting diodes

Funding: Leverhulme Trust (RPG-2017-231), the EPSRC NSF-CBET lead agency agreement (EP/R010595/1, 1706207), the DARPA NESD programme (N66001-17-C-4012) and the RS Macdonald Charitable Trust. C.M. acknowledges funding by the European Commission through a Marie Sklodowska-Curie Individual Fellowship (703387). Y. L. Deng acknowledges support from the Chinese Scholarship Council (CSC).Optogenetics, photostimulation of neural tissues rendered sensitive to light, is widely used in neuroscience to modulate the electrical excitability of neurons. For effective optical excitation of neurons, light wavelength and power density must fit with the expression levels and biophysical properties of the genetically encoded light‐sensitive ion channels used to confer light sensitivity on cells—most commonly, channelrhodopsins (ChRs). As light sources, organic light‐emitting diodes (OLEDs) offer attractive properties for miniaturized implantable devices for in vivo optical stimulation, but they do not yet operate routinely at the optical powers required for optogenetics. Here, OLEDs with doped charge transport layers are demonstrated that deliver blue light with good stability over millions of pulses, at powers sufficient to activate the ChR, CheRiff when expressed in cultured primary neurons, allowing live cell imaging of neural activity with the red genetically encoded calcium indicator, jRCaMP1a. Intracellular calcium responses scale with the radiant flux of OLED emission, when varied through changes in the current density, number of pulses, frequency, and pulse width delivered to the devices. The reported optimization and characterization of high‐power OLEDs are foundational for the development of miniaturized OLEDs with thin‐layer encapsulation on bioimplantable devices to allow single‐cell activation in vivo.Publisher PDFPeer reviewe

Demersal Fauna on Deep Seamounts of Sierra Leone Rise (Gulf of Guinea, Africa)

From January to March 2001 an experimental fishing survey was carried out on the Sierra Leone Rise by four Spanish commercial boats, with the aim of prospecting the fishing potential for longliners of the demersal resources inhabiting the seamounts located between 9ºN-5ºN and 19ºW-27ºW, at depths between 200 m and 1 000 m. A preliminary analysis of the data recorded shows that the demersal fish fauna composition was similar in three of the ten seamounts, with an absolute dominance of the alfonsino, Beryx splendens Lowe, 1838, which accounted for more than 90% of the total catch between 200 and 800 m depth. Other commercial species in catches were Beryx decadacthylus and some Scorpenidae. The size structure and the distribution of alfonsino oscillated between 27 and 52 cm showing an increase of the mean size with depth which is similar to the pattern found in other seamounts worldwide Major abundances were located at the northern surveyed seamount where the highest yields, up to 750 kg per 1 000 hooks, were obtained. The southernmost surveyed seamount exhibited the lowest abundances and was characterized by the absence of the alfonsino in the catches. The species richness of these deep communities was very low, the accompanying fauna comprising less than 30 species. Discarded fishes were, in order of abundance: Promethicthys prometeus, Coloconger cadenati, Polymixia nobilis, Ruvettus pretiosus, Etmopterus princeps, Serranus accraensis and Gephyroberyx darwini

ESTUDIO DE UNA ANTENA DE MICROCINTA FRACTAL TIPO E PARA LA BANDA DE LOS 2.4 GHZ

ResumenEn este trabajo, se presenta el estudio experimental y por simulación de una antena de parche basada en la geometría fractal tipo E para operar en la banda libre de los 2.4 GHz. La estructura electromagnética de la antena diseñada se analiza utilizando el simulador HFSS de ANSI, mientras que el prototipo experimental se caracteriza utilizando un analizador de redes de 6.5 GHz acoplado a un equipo de medición de campo cercano para medir los parámetros importantes de esta antena. Considerando la geometría fractal tipo E de dos iteraciones, los resultados en las simulaciones muestran que la antena diseñada presenta una frecuencia de resonancia de 2.463 GHz con pérdidas por retorno cercanas a -50 dB y un ancho de banda de acoplamiento de 74 MHz. Los parámetros correspondientes en el prototipo experimental resultaron ser de 2.624 GHz, -17 dB y 100 MHz, respectivamente. Estos resultados demuestran la factibilidad de utilizar la antena de microcinta fractal tipo E para aplicaciones en las comunicaciones inalámbricas para la banda de los 2.4 GHz.Palabras Claves: ancho de banda de acoplamiento, antenas de banda ancha, antenas de microcinta, bandas sin licencia, geometría fractal tipo E. STUDY OF AN ANTENNA OF FRACTAL MICROCINTA TYPE E FOR THE BAND OF THE 2.4 GHZAbstractIn this paper, the simulation and experimental study of an E-shape fractal patch antenna for the unlicensed band of 2.4 GHz is presented. The electromagnetic structure of this antenna is analyzed using the High Frequency Structure Simulator HFSS of ANSY, while the experimental antenna prototype is characterized using a network analyzer of 6.5 GHz and a (near-field based) antenna pattern measurement equipment. Simulation results show that the designed antenna presents a resonant frequency of 2.463 GHz with return losses equal to -50 dB, and a coupling bandwidth of 74 MHz. On the other hand, the corresponding experimental parameters are 2.56 GHz, -17 dB, and 100 MHz, respectively. The study performed in this paper demonstrates the suitability of using the E-shape fractal patch antenna for wireless applications at the 2.4 GHz unlicensed band.Keywords: broadband antennas, coupling bandwidth, ISM frequency bands, patch antennas, type-E fractal geometry

Kisspeptin Restores Pulsatile LH Secretion in Patients with Neurokinin B Signaling Deficiencies:Physiological, Pathophysiological and Therapeutic Implications

Pulsatile gonadotropin-releasing hormone (GnRH) is crucial to normal reproductive function and abnormalities in pulse frequency give rise to reproductive dysfunction. Kisspeptin and neurokinin B (NKB), neuropeptides secreted by the same neuronal population in the ventral hypothalamus, have emerged recently as critical central regulators of GnRH and thus gonadotropin secretion. Patients with mutations resulting in loss of signaling by either of these neuroendocrine peptides fail to advance through puberty but the mechanisms mediating this remain unresolved. We report here that continuous kisspeptin infusion restores gonadotropin pulsatility in patients with loss-of-function mutations in NKB (TAC3) or its receptor (TAC3R), indicating that kisspeptin on its own is sufficient to stimulate pulsatile GnRH secretion. Moreover, our findings suggest that NKB action is proximal to kisspeptin in the reproductive neuroendocrine cascade regulating GnRH secretion, and may act as an autocrine modulator of kisspeptin secretion. The ability of continuous kisspeptin infusion to induce pulsatile gonadotropin secretion further indicates that GnRH neurons are able to set up pulsatile secretion in the absence of pulsatile exogenous kisspeptin.Publisher PDFPeer reviewe