NGTS-11 b (TOI-1847 b): A Transiting Warm Saturn Recovered from a TESS Single-transit Event

We report the discovery of NGTS-11 b (=TOI-1847 b), a transiting Saturn in a 35.46-day orbit around a mid K-type star (Teff=5050 K). We initially identified the system from a single-transit event in a TESS full-frame image light-curve. Following seventy-nine nights of photometric monitoring with an NGTS telescope, we observed a second full transit of NGTS-11 b approximately one year after the TESS single-transit event. The NGTS transit confirmed the parameters of the transit signal and restricted the orbital period to a set of 13 discrete periods. We combined our transit detections with precise radial velocity measurements to determine the true orbital period and measure the mass of the planet. We find NGTS-11 b has a radius of 0.817+0.028-0.032 $R_J$, a mass of 0.344+0.092-0.073 $M_J$, and an equilibrium temperature of just 435+34-32 K, making it one of the coolest known transiting gas giants. NGTS-11 b is the first exoplanet to be discovered after being initially identified as a TESS single-transit event, and its discovery highlights the power of intense photometric monitoring in recovering longer-period transiting exoplanets from single-transit events

Acidic Digestion in a Teleost: Postprandial and Circadian Pattern of Gastric pH, Pepsin Activity, and Pepsinogen and Proton Pump mRNAs Expression

Two different modes for regulation of stomach acid secretion have been described in vertebrates. Some species exhibit a continuous acid secretion maintaining a low gastric pH during fasting. Others, as some teleosts, maintain a neutral gastric pH during fasting while the hydrochloric acid is released only after the ingestion of a meal. Those different patterns seem to be closely related to specific feeding habits. However, our recent observations suggest that this acidification pattern could be modified by changes in daily feeding frequency and time schedule. The aim of this study was to advance in understanding the regulation mechanisms of stomach digestion and pattern of acid secretion in teleost fish. We have examined the postprandial pattern of gastric pH, pepsin activity, and mRNA expression for pepsinogen and proton pump in white seabream juveniles maintained under a light/dark 12/12 hours cycle and receiving only one morning meal. The pepsin activity was analyzed according to the standard protocol buffering at pH 2 and using the actual pH measured in the stomach. The results show how the enzyme precursor is permanently available while the hydrochloric acid, which activates the zymogen fraction, is secreted just after the ingestion of food. Results also reveal that analytical protocol at pH 2 notably overestimates true pepsin activity in fish stomach. The expression of the mRNA encoding pepsinogen and proton pump exhibited almost parallel patterns, with notable increases during the darkness period and sharp decreases just before the morning meal. These results indicate that white seabream uses the resting hours for recovering the mRNA stock that will be quickly used during the feeding process. Our data clearly shows that both daily illumination pattern and feeding time are involved at different level in the regulation of the secretion of digestive juices

Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in response to repeated intermittent MDMA administration in adolescent rats

<p>Abstract</p> <p>Background</p> <p>Many studies have focused on the implication of the serotonin and dopamine systems in neuroadaptive responses to the recreational drug 3,4-methylenedioxy-metamphetamine (MDMA). Less attention has been given to the major excitatory neurotransmitter glutamate known to be implicated in schizophrenia and drug addiction. The aim of the present study was to investigate the effect of repeated intermittent MDMA administration upon gene-transcript expression of the glutamate transporters (EAAT1, EAAT2-1, EAAT2-2), the glutamate receptor subunits of AMPA (GluR1, GluR2, GluR3), the glutamate receptor subunits of NMDA (NR1, NR2A and NR2B), as well as metabotropic glutamate receptors (mGluR1, mGluR2, mGluR3, mGluR5) in six different brain regions. Adolescent male Sprague Dawley rats received MDMA at the doses of 3 × 1 and 3 × 5 mg/kg/day, or 3× vehicle 3 hours apart, every 7^thday for 4 weeks. The gene-transcript levels were assessed using real-time PCR validated with a range of housekeeping genes.</p> <p>Results</p> <p>The findings showed pronounced enhancements in gene-transcript expression of GluR2, mGluR1, mGluR5, NR1, NR2A, NR2B, EAAT1, and EAAT2-2 in the cortex at bregma +1.6. In the caudate putamen, mRNA levels of GluR3, NR2A, and NR2B receptor subunits were significantly increased. In contrast, the gene-transcript expression of GluR1 was reduced in the hippocampus. In the hypothalamus, there was a significant increase of GluR1, GluR3, mGluR1, and mGluR3 gene-transcript expressions.</p> <p>Conclusion</p> <p>Repeated intermittent MDMA administration induces neuroadaptive changes in gene-transcript expressions of glutamatergic NMDA and AMPA receptor subunits, metabotropic receptors and transporters in regions of the brain regulating reward-related associative learning, cognition, and memory and neuro-endocrine functions.</p

NEDD9 Is a Positive Regulator of Epithelial-Mesenchymal Transition and Promotes Invasion in Aggressive Breast Cancer

Epithelial to mesenchymal transition (EMT) plays an important role in many biological processes. The latest studies revealed that aggressive breast cancer, especially the triple-negative breast cancer (TNBC) subtype was frequently associated with apparent EMT, but the mechanisms are still unclear. NEDD9/HEF1/Cas-L is a member of the Cas protein family and was identified as a metastasis marker in multiple cancer types. In this study, we wished to discern the role of NEDD9 in breast cancer progression and to investigate the molecular mechanism by which NEDD9 regulates EMT and promotes invasion in triple-negative breast cancer. We showed that expression of NEDD9 was frequently upregulated in TNBC cell lines, and in aggressive breast tumors, especially in TNBC subtype. Knockdown of endogenous NEDD9 reduced the migration, invasion and proliferation of TNBC cells. Moreover, ectopic overexpression of NEDD9 in mammary epithelial cells led to a string of events including the trigger of EMT, activation of ERK signaling, increase of several EMT-inducing transcription factors and promotion of their interactions with the E-cadherin promoter. Data presented in this report contribute to the understanding of the mechanisms by which NEDD9 promotes EMT, and provide useful clues to the evaluation of the potential of NEDD9 as a responsive molecular target for TNBC chemotherapy

Identifying New Therapeutic Targets via Modulation of Protein Corona Formation by Engineered Nanoparticles

We introduce a promising methodology to identify new therapeutic targets in cancer. Proteins bind to nanoparticles to form a protein corona. We modulate this corona by using surface-engineered nanoparticles, and identify protein composition to provide insight into disease development.Using a family of structurally homologous nanoparticles we have investigated the changes in the protein corona around surface-functionalized gold nanoparticles (AuNPs) from normal and malignant ovarian cell lysates. Proteomics analysis using mass spectrometry identified hepatoma-derived growth factor (HDGF) that is found exclusively on positively charged AuNPs ((+)AuNPs) after incubation with the lysates. We confirmed expression of HDGF in various ovarian cancer cells and validated binding selectivity to (+)AuNPs by Western blot analysis. Silencing of HDGF by siRNA resulted s inhibition in proliferation of ovarian cancer cells.We investigated the modulation of protein corona around surface-functionalized gold nanoparticles as a promising approach to identify new therapeutic targets. The potential of our method for identifying therapeutic targets was demonstrated through silencing of HDGF by siRNA, which inhibited proliferation of ovarian cancer cells. This integrated proteomics, bioinformatics, and nanotechnology strategy demonstrates that protein corona identification can be used to discover novel therapeutic targets in cancer

Spread of Epidemic MRSA-ST5-IV Clone Encoding PVL as a Major Cause of Community Onset Staphylococcal Infections in Argentinean Children

BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus-(CA-MRSA) strains have emerged in Argentina. We investigated the clinical and molecular evolution of community-onset MRSA infections (CO-MRSA) in children of Córdoba, Argentina, 2005-2008. Additionally, data from 2007 were compared with the epidemiology of these infections in other regions of the country. METHODOLOGY/PRINCIPAL FINDINGS: Two datasets were used: i) lab-based prospective surveillance of CA-MRSA isolates from 3 Córdoba pediatric hospitals-(CBAH1-H3) in 2007-2008 (compared to previously published data of 2005) and ii) a sampling of CO-MRSA from a study involving both, healthcare-associated community-onset-(HACO) infections in children with risk-factors for healthcare-associated infections-(HRFs), and CA-MRSA infections in patients without HRFs detected in multiple centers of Argentina in 2007. Molecular typing was performed on the CA-MRSA-(n: 99) isolates from the CBAH1-H3-dataset and on the HACO-MRSA-(n: 51) and CA-MRSA-(n: 213) isolates from other regions. Between 2005-2008, the annual proportion of CA-MRSA/CA-S. aureus in Córdoba hospitals increased from 25% to 49%, P<0.01. Total CA-MRSA infections increased 3.6 fold-(5.1 to 18.6 cases/100,000 annual-visits, P<0.0001), associated with an important increase of invasive CA-MRSA infections-(8.5 fold). In all regions analyzed, a single genotype prevailed in both CA-MRSA (82%) and HACO-MRSA(57%), which showed pulsed-field-gel electrophoresis-(PFGE)-type-"I", sequence-type-5-(ST5), SCCmec-type-IVa, spa-t311, and was positive for PVL. The second clone, pulsotype-N/ST30/CC30/SCCmecIVc/t019/PVL(+), accounted for 11.5% of total CA-MRSA infections. Importantly, the first 4 isolates of Argentina belonging to South American-USA300 clone-(USA300/ST8/CC8/SCCmecIVc/t008/PVL(+)/ACME(-)) were detected. We also demonstrated that a HA-MRSA clone-(pulsotype-C/ST100/CC5) caused 2% and 10% of CA-MRSA and HACO-MRSA infections respectively and was associated with a SCCmec type closely related to SCCmecIV(2B&5). CONCLUSIONS/SIGNIFICANCE: The dissemination of epidemic MRSA clone, ST5-IV-PVL(+) was the main cause of increasing staphylococcal community-onset infections in Argentinean children (2003-2008), conversely to other countries. The predominance of this clone, which has capacity to express the h-VISA phenotype, in healthcare-associated community-onset cases suggests that it has infiltrated into hospital-settings

Lymphatic vessel density and function in experimental bladder cancer

<p>Abstract</p> <p>Background</p> <p>The lymphatics form a second circulatory system that drains the extracellular fluid and proteins from the tumor microenvironment, and provides an exclusive environment in which immune cells interact and respond to foreign antigen. Both cancer and inflammation are known to induce lymphangiogenesis. However, little is known about bladder lymphatic vessels and their involvement in cancer formation and progression.</p> <p>Methods</p> <p>A double transgenic mouse model was generated by crossing a bladder cancer-induced transgenic, in which SV40 large T antigen was under the control of uroplakin II promoter, with another transgenic mouse harboring a <it>lacZ </it>reporter gene under the control of an NF-κB-responsive promoter (κB-<it>lacZ</it>) exhibiting constitutive activity of β-galactosidase in lymphatic endothelial cells. In this new mouse model (SV40-<it>lacZ</it>), we examined the lymphatic vessel density (LVD) and function (LVF) during bladder cancer progression. LVD was performed in bladder whole mounts and cross-sections by fluorescent immunohistochemistry (IHC) using LYVE-1 antibody. LVF was assessed by real-time <it>in vivo </it>imaging techniques using a contrast agent (biotin-BSA-Gd-DTPA-Cy5.5; Gd-Cy5.5) suitable for both magnetic resonance imaging (MRI) and near infrared fluorescence (NIRF). In addition, IHC of Cy5.5 was used for time-course analysis of co-localization of Gd-Cy5.5 with LYVE-1-positive lymphatics and CD31-positive blood vessels.</p> <p>Results</p> <p>SV40-<it>lacZ </it>mice develop bladder cancer and permitted visualization of lymphatics. A significant increase in LVD was found concomitantly with bladder cancer progression. Double labeling of the bladder cross-sections with LYVE-1 and Ki-67 antibodies indicated cancer-induced lymphangiogenesis. MRI detected mouse bladder cancer, as early as 4 months, and permitted to follow tumor sizes during cancer progression. Using Gd-Cy5.5 as a contrast agent for MRI-guided lymphangiography, we determined a possible reduction of lymphatic flow within the tumoral area. In addition, NIRF studies of Gd-Cy5.5 confirmed its temporal distribution between CD31-positive blood vessels and LYVE-1 positive lymphatic vessels.</p> <p>Conclusion</p> <p>SV40-<it>lacZ </it>mice permit the visualization of lymphatics during bladder cancer progression. Gd-Cy5.5, as a double contrast agent for NIRF and MRI, permits to quantify delivery, transport rates, and volumes of macromolecular fluid flow through the interstitial-lymphatic continuum. Our results open the path for the study of lymphatic activity <it>in vivo </it>and in real time, and support the role of lymphangiogenesis during bladder cancer progression.</p

An ultrahot Neptune in the Neptune desert

About one out of 200 Sun-like stars has a planet with an orbital period shorter than one day: an ultra-short-period planet (Sanchis-ojeda et al. 2014; Winn et al. 2018). All of the previously known ultra-short-period planets are either hot Jupiters, with sizes above 10 Earth radii (Re), or apparently rocky planets smaller than 2 Re. Such lack of planets of intermediate size (the "hot Neptune desert") has been interpreted as the inability of low-mass planets to retain any hydrogen/helium (H/He) envelope in the face of strong stellar irradiation. Here, we report the discovery of an ultra-short-period planet with a radius of 4.6 Re and a mass of 29 Me, firmly in the hot Neptune desert. Data from the Transiting Exoplanet Survey Satellite (Ricker et al. 2015) revealed transits of the bright Sun-like star \starname\, every 0.79 days. The planet's mean density is similar to that of Neptune, and according to thermal evolution models, it has a H/He-rich envelope constituting 9.0^(+2.7)_(-2.9)% of the total mass. With an equilibrium temperature around 2000 K, it is unclear how this "ultra-hot Neptune" managed to retain such an envelope. Follow-up observations of the planet's atmosphere to better understand its origin and physical nature will be facilitated by the star's brightness (Vmag=9.8)

Age and date for early arrival of the Acheulian in Europe (Barranc de la Boella, la Canonja, Spain)

The first arrivals of hominin populations into Eurasia during the Early Pleistocene are currently considered to have occurred as short and poorly dated biological dispersions. Questions as to the tempo and mode of these early prehistoric settlements have given rise to debates concerning the taxonomic significance of the lithic assemblages, as trace fossils, and the geographical distribution of the technological traditions found in the Lower Palaeolithic record. Here, we report on the Barranc de la Boella site which has yielded a lithic assemblage dating to ,1 million years ago that includes large cutting tools (LCT). We argue that distinct technological traditions coexisted in the Iberian archaeological repertoires of the late Early Pleistocene age in a similar way to the earliest sub-Saharan African artefact assemblages. These differences between stone tool assemblages may be attributed to the different chronologies of hominin dispersal events. The archaeological record of Barranc de la Boella completes the geographical distribution of LCT assemblages across southern Eurasia during the EMPT (Early-Middle Pleistocene Transition, circa 942 to 641 kyr). Up to now, chronology of the earliest European LCT assemblages is based on the abundant Palaeolithic record found in terrace river sequences which have been dated to the end of the EMPT and later. However, the findings at Barranc de la Boella suggest that early LCT lithic assemblages appeared in the SW of Europe during earlier hominin dispersal episodes before the definitive colonization of temperate Eurasia took place.The research at Barranc de la Boella has been carried out with the financial support of the Spanish Ministerio de Economı´a y Competitividad (CGL2012- 36682; CGL2012-38358, CGL2012-38434-C03-03 and CGL2010-15326; MICINN project HAR2009-7223/HIST), Generalitat de Catalunya, AGAUR agence (projects 2014SGR-901; 2014SGR-899; 2009SGR-324, 2009PBR-0033 and 2009SGR-188) and Junta de Castilla y Leo´n BU1004A09. Financial support for Barranc de la Boella field work and archaeological excavations is provided by the Ajuntament de la Canonja and Departament de Cultura (Servei d’Arqueologia i Paleontologia) de la Generalitat de Catalunya. A. Carrancho’s research was funded by the International Excellence Programme, Reinforcement subprogramme of the Spanish Ministry of Education. I. Lozano-Ferna´ndez acknowledges the pre-doctoral grant from the Fundacio´n Atapuerca. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript