Context.
Large sub-Neptunes are uncommon around the coolest stars in the Galaxy and are rarer still around those that are metal-poor. However, owing to the large planet-to-star radius ratio, these ...planets are highly suitable for atmospheric study via transmission spectroscopy in the infrared, such as with JWST.
Aims.
Here we report the discovery and validation of a sub-Neptune orbiting the thick-disk, mid-M dwarf star TOI-2406. The star’s low metallicity and the relatively large size and short period of the planet make TOI-2406 b an unusual outcome of planet formation, and its characterisation provides an important observational constraint for formation models.
Methods.
We first infer properties of the host star by analysing the star’s near-infrared spectrum, spectral energy distribution, and
Gaia
parallax. We use multi-band photometry to confirm that the transit event is on-target and achromatic, and we statistically validate the TESS signal as a transiting exoplanet. We then determine physical properties of the planet through global transit modelling of the TESS and ground-based time-series data.
Results.
We determine the host to be a metal-poor M4 V star, located at a distance of 56 pc, with properties
T
eff
= 3100 ± 75 K,
M
*
= 0.162 ± 0.008
M
⊙
,
R
*
= 0.202 ± 0.011
R
⊙
, and Fe∕H = −0.38 ± 0.07, and a member of the thick disk. The planet is a relatively large sub-Neptune for the M-dwarf planet population, with
R
p
= 2.94 ± 0.17
R
⊕
and
P
= 3.077 d, producing transits of 2% depth. We note the orbit has a non-zero eccentricity to 3
σ
, prompting questions about the dynamical history of the system.
Conclusions.
This system is an interesting outcome of planet formation and presents a benchmark for large-planet formation around metal-poor, low-mass stars. The system warrants further study, in particular radial velocity follow-up to determine the planet mass and constrain possible bound companions. Furthermore, TOI-2406 b is a good target for future atmospheric study through transmission spectroscopy. Although the planet’s mass remains to be constrained, we estimate the S/N using amass-radius relationship, ranking the system fifth in the population of large sub-Neptunes, with TOI-2406 b having a much lower equilibrium temperature than other spectroscopically accessible members of this population.
Headache is a common reason to visit the emergency department (ED). Tension-type headache (TTH) is the commonest headache. The diagnosis of TTH implies a mild condition, with no need for special ...tests. We evaluated the use of the International Classification of Headache Disorders (ICHD) criteria for TTH in the ED. We performed a cross-sectional study including all ED patients with a definite TTH diagnosis in their discharge report for 2.5 years. We evaluated whether the ICHD criteria for TTH were referenced and met. We analysed discrepancies concerning anamnesis or prior history and reclassified patients. A total of 211 out of 2132 patients fulfilled the criteria (9.9%). Only five patients fulfilled TTH criteria. Criteria A-D were referenced in 60-84% of patients and met in 16-74% of these patients. Anamnesis was discrepant in 87.5% as was prior history in 20.8%. After re-reclassification, 21 patients fulfilled the criteria for TTH (five) or probable TTH (16). In 106 patients, another headache was diagnosed, with migraine in 40 (18.9%), secondary headache in 64 (30.3%), and a life-threatening disorder in 13 (6.1%). In our sample, TTH was overdiagnosed. Only a minority of patients fulfilled the ICHD criteria. Inconsistencies in prior medical history or anamnesis were frequent.
Alterations in connexin 43 (Cx43) expression and/or gap junction (GJ)-mediated intercellular communication are implicated in cancer pathogenesis. Herein, we have investigated the role of Cx43 in ...melanoma cell proliferation and apoptosis sensitivity in vitro, as well as metastatic capability and tumour growth in vivo.
Connexin 43 expression levels, GJ coupling and proliferation rates were analysed in four different human melanoma cell lines. Furthermore, tumour growth and lung metastasis of high compared with low Cx43-expressing FMS cells were evaluated in vivo using a melanoma xenograft model.
Specific inhibition of Cx43 channel activity accelerated melanoma cell proliferation, whereas overexpression of Cx43 increased GJ coupling and reduced cell growth. Moreover, Cx43 overexpression in FMS cells increased basal and tumour necrosis factor-α-induced apoptosis and resulted in decreased melanoma tumour growth and lower number and size of metastatic foci in vivo.
Our findings reveal an important role for Cx43 in intrinsically controlling melanoma growth, death and metastasis, and emphasise the potential use of compounds that selectively enhance Cx43 expression on melanoma in the future chemotherapy and/or immunotherapy protocols.
Context.
Thanks to the relative ease of finding and characterizing small planets around M-dwarf stars, these objects have become cornerstones in the field of exoplanet studies. The current paucity of ...planets in long-period orbits around M dwarfs makes such objects particularly compelling as they provide clues about the formation and evolution of these systems.
Aims.
In this study we present the discovery of TOI-2257 b (TIC 198485881), a long-period (35 d) sub-Neptune orbiting an M3 star at 57.8 pc. Its transit depth is about 0.4%, large enough to be detected with medium-size, ground-based telescopes. The long transit duration suggests the planet is in a highly eccentric orbit (
e
~ 0.5), which would make it the most eccentric planet known to be transiting an M-dwarf star.
Methods.
We combined TESS and ground-based data obtained with the 1.0-meter SAINT-EX, 0.60-meter TRAPPIST-North, and 1.2-meter FLWO telescopes to find a planetary size of 2.2
R
⊕
and an orbital period of 35.19 days. In addition, we make use of archival data, high-resolution imaging, and vetting packages to support our planetary interpretation.
Results.
With its long period and high eccentricity, TOI-2257 b falls into a novel slice of parameter space. Despite the planet’s low equilibrium temperature (~256 K), its host star’s small size (
R
*
= 0.311 ± 0.015) and relative infrared brightness (
K
mag
= 10.7) make it a suitable candidate for atmospheric exploration via transmission spectroscopy.
The Mar Menor (SE Spain), the largest hypersaline coastal lagoon of the Mediterranean basin, suffers a severe eutrophication crisis due to the nutrients that receives from the Campo de Cartagena ...watershed, mainly nitrate from intensive agriculture. This paper updates the state of the art in relation with nutrient discharges to the Mar Menor, and summarizes results from different tested Nature-Based Solution (NBS). Specifically, we show i) results from a pilot plant with woodchip bioreactors for nitrate-enriched brine denitrification, and ii) the first results obtained in a pilot plant with bioreactors and constructed wetlands for treatment of agricultural drainage water and leachates, as well as other effluents. Nutrient discharges to the lagoon are highly variable and occur via drainage network, drains, stormwater pipes, direct groundwater discharges from the Quaternary aquifer, and others. For instance, between January 2017 and January 2018 measured daily superficial discharge (floods excluded) ofN-NO3− amounted from 119 kg d−1 to 1084 kg d−1. Estimations subsurface discharges ranged 815 to 3836 kg N-NO3− d−1 in 2018–2020. Field studies in coastal wetlands (e.g. inflow ≈20–30 mg N-NO3− L−1, removal ≈80–90%) and results from pilot plants with bioreactors (e.g. inflow ≈30–40 mg N-NO3− L−1, removal ≈90–95%) and constructed wetlands (e.g. inflow ≈30–40 mg N-NO3− L−1, removal ≈60–70%), showed the good performance of these systems for nutrient retention. Four strategies are considered for reducing nutrient inputs into the Mar Menor, which include a combination of nature-based solutions and best management practices. (i) Reducing the leaching of nitrate to the aquifer and export of nutrients and sediments following heavy rains by improving fertilization, and irrigation routines, and soil conservation measures in the agricultural fields. (ii) Development of effective and scalable tools for denitrification of nitrate-rich brine produced by on-farm desalination plants. (iii) Capture and treatment of polluted water discharged to the Mar Menor via hydrologic networks, subsurface flow, drainage ditches, and others. (iv) Preservation and restoration of coastal wetlands.
Display omitted
•Mar Menor receives nutrients, mainly from agricultural discharges.•Coastal wetlands acts as buffers protecting the Mar Menor from nutrient inputs.•Bioreactors and CWs are recommended BMP for treatment of nutrient enriched discharges.•In the Campo de Cartagena BMP should be addressed on a watershed scale.•BMP should address fertilization and irrigation protocols and soil conservation.
We report the characterization of two planet candidates detected by the Transiting Exoplanet Survey Satellite (TESS), TOI-1199 b and TOI-1273 b, with periods of 3.7 and 4.6 days, respectively. ...Follow-up observations for both targets, which include several ground-based light curves, confirmed the transit events. High-precision radial velocities from the SOPHIE spectrograph revealed signals at the expected frequencies and phases of the transiting candidates and allowed mass determinations with a precision of 8.4% and 6.7% for TOI-1199 b and TOI-1273 b, respectively. The planetary and orbital parameters were derived from a joint analysis of the radial velocities and photometric data. We find that the planets have masses of 0.239 ± 0.020 M J and 0.222 ± 0.015 M J and radii of 0.938 ± 0.025 R J and 0.99 ± 0.22 R J , respectively. The grazing transit of TOI-1273 b translates to a larger uncertainty in its radius, and hence also in its bulk density, compared to TOI-1199 b. The inferred bulk densities of 0.358 ± 0.041 g cm −3 and 0.28 ± 0.11 g cm −3 are among the lowest known for exoplanets in this mass range, which, considering the brightness of the host stars ( V ≈11 mag), render them particularly amenable to atmospheric characterization via the transit spectroscopy technique. The better constraints on the parameters of TOI-1199 b provide a transmission spectroscopy metric of 134 ± 17, making it the better suited of the two planets for atmospheric studies.
We report the discovery of a hot Jupiter on a 3.28-day orbit around a 1.08
M
⊙
G0 star that is the secondary component in a loose binary system. Based on follow-up radial velocity observations of ...TOI-858 B with CORALIE on the Swiss 1.2 m telescope and CHIRON on the 1.5 m telescope at the Cerro Tololo Inter-American Observatory (CTIO), we measured the planet mass to be 1.10
−0.07
+0.08
M
J
. Two transits were further observed with CORALIE to determine the alignment of TOI-858 B b with respect to its host star. Analysis of the Rossiter-McLaughlin signal from the planet shows that the sky-projected obliquity is
λ
= 99.3
−3.7
+3.8°
. Numerical simulations show that the neighbour star TOI-858 A is too distant to have trapped the planet in a Kozai–Lidov resonance, suggesting a different dynamical evolution or a primordial origin to explain this misalignment. The 1.15
M
⊙
primary F9 star of the system (TYC 8501-01597-1, at
ρ
~11″) was also observed with CORALIE in order to provide upper limits for the presence of aplanetary companion orbiting that star.
Kallikrein-related peptidases (KLKs) are a family of serine proteases that have been shown to be dysregulated in several malignancies including ovarian cancer. The control of kallikrein genes and ...their physiological function in cancer is not well understood. We hypothesized that microRNAs (miRNAs) represent a novel mechanism for post-transcriptional control of KLK expression in cancer.
We first analysed miRNA expression in ovarian cancer in silico. A total of 98 miRNAs were reported to have altered expression in ovarian cancer. Three of these miRNAs were predicted to target KLK10. We experimentally verified the predicted miR-KLK10 interaction using two independent techniques, a luciferase assay with a construct containing the KLK10 3' untranslated region (UTR), pMIR-KLK10, and measuring KLK10 protein levels after transfection with miRNA.
When we co-transfected cells with pMIR-KLK10 and either let-7f, miR-224, or mR-516a, we saw decreased luciferase signal, suggesting that these miRNAs can target KLK10. We then examined the effect of these three miRNAs on KLK10 protein expression and cell growth. Transfection of all miRNAs, let-7f, miR-224, and miR-516a led to a decrease in protein expression and cellular growth. This effect was shown to be dose dependent. The KLK10 protein levels were partially restored by co-transfecting let-7f and its inhibitor. In addition, there was a slight decrease in KLK10 mRNA expression after transfection with let-7f.
Our results confirm that KLKs can be targeted by more than one miRNA. Increased expression of certain miRNAs in ovarian cancer can lead to decreased KLK protein expression and subsequently have a negative effect on cell proliferation. This dose-dependent effect suggests that a 'tweaking' or 'fine-tuning' mechanism exists in which the expression of one KLK can be controlled by multiple miRNAs. These data together suggest that miRNA may be used as potential therapeutic options and further studies are required.
Randomised trials comparing the efficacy of standard endocrine therapy (ET) versus experimental ET + bevacizumab (Bev) in 1st line hormone receptor–positive patients with metastatic breast cancer ...have thus far shown conflicting results.
We pooled data from two similar phase III randomised trials of ET ± Bev (LEA and Cancer and Leukemia Group B 40503) to increase precision in estimating treatment effect. Primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Exploratory analyses were performed within subgroups defined by patients with recurrent disease, de novo disease, prior endocrine sensitivity or resistance and reported grades III–IV hypertension and proteinuria.
The pooled sample consisted of 749 patients randomised to ET or ET + Bev. Median PFS was 14.3 months for ET versus 19 months for ET + Bev (unadjusted hazard ratio HR 0.77; 95% confidence interval CI 0.66–0.91; p < 0.01). ORR and CBR with ET and ET + Bev were 40 versus 61% (p < 0.01) and 64 versus 77% (p < 0.01), respectively. There was no difference in OS (HR 0.96; 95% CI 0.77–1.18; p = 0.68). PFS was superior for ET + Bev for endocrine-sensitive patients (HR 0.68; 95% CI 0.53–0.89; p = 0.004). Grade III–IV hypertension (2.2 versus 20.1%), proteinuria (0 versus 9.3%), cardiovascular (0.5 versus 4.2%) and liver events (0 versus 2.9%) were significantly higher for ET + Bev (all p < 0.01). Hypertension and proteinuria were not predictors of efficacy (interaction test p = 0.33).
The addition of Bev to ET increased PFS overall and in endocrine-sensitive patients but not OS at the expense of significant additional toxicity.
ClinicalTrial.Gov NCT00545077 and NCT00601900.
•Bevacizumab plus endocrine therapy increased progression-free survival overall.•Bevacizumab plus endocrine therapy does not increased overall survival.•This combination adds significant toxicity.•This should not be recommended for 1st line HR+/HER2-advanced breast cancer.•Hypertension and proteinuria are not predictive of bevacizumab efficacy.
The Transiting Exoplanet Survey Satellite (TESS) mission was designed to perform an all-sky search of planets around bright and nearby stars. Here we report the discovery of two sub-Neptunes orbiting ...around TOI 1062 (TIC 299799658), a V = 10.25 G9V star observed in the TESS Sectors 1, 13, 27, and 28. We use precise radial velocity observations from HARPS to confirm and characterize these two planets. TOI 1062b has a radius of 2.265(-0.091,+0.096) Rꚛ, a mass of 10.15 ± 0.8 Mꚛ, and an orbital period of 4.1130 ± 0.0015 days. The second planet is not transiting, has a minimum mass of 9.78(−1.18,+1.26) Mꚛ and is near the 2:1 mean motion resonance with the innermost planet with an orbital period of 7.972(−0.024,+0.018) days. We performed a dynamical analysis to explore the proximity of the system to this resonance, and to attempt further constraining the orbital parameters. The transiting planet has a mean density of 4.85(−0.74,+0.84) g/cu. cm and an analysis of its internal structure reveals that it is expected to have a small volatile envelope accounting for 0.35% of the mass at most. The star’s brightness and the proximity of the inner planet to what is know as the radius gap make it an interesting candidate for transmission spectroscopy, which could further constrain the composition and internal structure of TOI 1062b.
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