The
Acremonium chrysogenum cephalosporin biosynthetic genes are divided in two different clusters. The central step of the biosynthetic pathway (epimerization of isopenicillin N to penicillin N) ...occurs in peroxisomes. We found in the “early” cephalosporin cluster a new ORF encoding a regulatory protein (CefR), containing a nuclear targeting signal and a “Fungal_trans” domain. Targeted inactivation of
cefR delays expression of the
cefEF gene, increases penicillin N secretion and decreases cephalosporin production. Overexpression of the
cefR gene decreased (up to 60%) penicillin N secretion, saving precursors and resulting in increased cephalosporin C production. Northern blot analysis revealed that the CefR protein acts as a repressor of the exporter
cefT and exerts a small stimulatory effect over the expression level of
cefEF that explains the increased cephalosporin yields observed in transformants overexpressing
cefR. In summary, we describe for the first time a modulator of beta-lactam intermediate transporters in
A. chrysogenum.
► A regulatory gene cefR modulates cephalosporin biosynthesis. ► Inactivation of CefR increases PenN secretion and decreases CPC. ► CefR controls expression of cefT and cefEF. ► In summary, CefR saves intermediates for CPC production.
Spontaneous neuronal activity is essential to neural development. Until recently, neurons were believed to be the only excitable cells to display spontaneous activity. However, cultured astrocytes ...and, more recently, astrocytes in situ are now known to exhibit spontaneous Ca2+ transients. Here we used Ca2+ imaging of astrocytes from transgenic mice for the simultaneous monitoring of Ca2+i changes in large numbers of astrocytes. We found that spontaneous activity is a common property of most brain astrocytes that is lost in response to a lesion. These spontaneous Ca2+i oscillations require extracellular and intracellular Ca2+. Moreover, network analysis revealed that most astrocytes formed correlated networks of dozens of these cells, which were synchronous with both astrocytes and neurons. We found that decreasing spontaneous Ca2+i transients in neurons by TTX does not alter the number of active astrocytes, although it impairs their synchronous network activity. Conversely, bicuculline-induced epileptic patterns of Ca2+i transients in neurons cause an increase in the number of active astrocytes and in their network synchrony. Furthermore, activation of non-NMDA and NMDA ionotropic glutamate receptors is required to correlate astrocytic networks. These results show that spontaneous activity in astrocytes and neurons is patterned into correlated neuronal/astrocytic networks in which neuronal activity regulates the network properties of astrocytes. This network activity may be essential for neural development and synaptic plasticity.
We aimed to describe and characterize the gut microbiota composition and diversity in children with obesity according to their metabolic health status.
Anthropometry, Triglycerides, HDL cholesterol, ...HOMA-IR, and systolic and diastolic blood pressure (SBP, DBP) were evaluated (and z-score calculated) and faecal samples were collected from 191 children with obesity aged from 8 to 14. All children were classified depending on their cardiometabolic status in either a “metabolically healthy” (MHO; n = 106) or “metabolically unhealthy” (MUO; n = 85) group. Differences in gut microbiota taxonomies and diversity between groups (MUO vs MHO) were analysed. Alpha diversity index was calculated as Chao1 and Simpson’s index, and β-diversity was calculated as Adonis Bray–Curtis index. Spearman’s correlations and logistic regressions were performed to study the association between cardiometabolic health and the microbiota.
Children in the MUO presented significantly lower alpha diversity and richness than those in the MHO group (Chao1 index p = 0.021, Simpson’s index p = 0.045, respectively), whereas microbiota β-diversity did not differ by the cardiometabolic health status (Adonis Bray–Curtis, R2 = 0.006; p = 0.155). The MUO group was characterized by lower relative abundances of the genera Christensenellaceae R7 group (MHO:1.42% 0.21–2.94; MUO:0.47% 0.02–1.60, p < 0.004), and Akkermansia (MHO:0.26% 0.01–2.19; MUO:0.01% 0.00–0.36, p < 0.001) and higher relative abundances of Bacteroides (MHO:10.6% 4.64–18.5; MUO:17.0% 7.18–27.4, p = 0.012) genus. After the adjustment by sex, age, and BMI, higher Akkermansia (OR: 0.86, CI: 0.75–0.97; p = 0.033), Christensenellaceae R7 group (OR: 0.86, 95% CI: 075–0.98; p = 0.031) and Chao1 index (OR: 0.86, CI: 0.96–1.00; p = 0.023) represented a lower risk of the presence of one or more altered cardiovascular risk factors.
Lower proportions of Christensenellaceae and Akkermansia and lower diversity and richness seem to be indicators of a metabolic unhealthy status in children with obesity.
Context.
Exoplanets with orbital periods of less than one day are known as ultra-short period (USP) planets. They are relatively rare products of planetary formation and evolution processes, but ...especially favourable for characterisation with current planet detection methods. At the time of writing, 125 USP planets have already been confirmed.
Aims.
Our aim is to validate the planetary nature of two new transiting planet candidates around M dwarfs announced by the NASA Transiting Exoplanet Survey Satellite (TESS), registered as TESS Objects of Interest (TOIs) TOI-1442.01 and TOI-2445.01.
Methods.
We used TESS data, ground-based photometric light curves, and Subaru/IRD spectrograph radial velocity (RV) measurements to validate both planetary candidates and to establish their physical properties.
Results.
TOI-1442 bis a validated exoplanet with an orbital period of
P
= 0.4090682 ± 0.0000004 day, a radius of
R
p
= 1.15 ± 0.06
R
⊕
, and equilibrium temperature of
T
p,eq
= 1357
−42
+49
K. TOI-2445 b is also validated with an orbital period of
P
= 0.3711286 ± 0.0000004 day, a radius of
R
p
= 1.33 ± 0.09
R
⊕
, and equilibrium temperature of
T
p,eq
= 1330
−56
+61
K. Their physical properties align with current empirical trends and formation theories of USP planets. Based on the RV measurements, we set 3
σ
upper mass limits of 8
M
⊕
and 20
M
⊕
, thus confirming the non-stellar, sub-Jovian nature of both transiting objects. More RV measurements will be needed to constrain the planetary masses and mean densities, and the predicted presence of outer planetary companions. These targets extend the small sample of USP planets orbiting around M dwarfs up to 21 members. They are also among the 20 most suitable terrestrial planets for atmospheric characterisation via secondary eclipse with the
James Webb
Space Telescope, according to a widespread emission spectroscopy metric.
We report the discovery of a Neptune-like planet (LP 714-47 b,
P
= 4.05204 d,
m
b
= 30.8 ± 1.5
M
⊕
,
R
b
= 4.7 ± 0.3
R
⊕
) located in the “hot Neptune desert”. Confirmation of the TESS Object of ...Interest (TOI 442.01) was achieved with radial-velocity follow-up using CARMENES, ESPRESSO, HIRES, iSHELL, and PFS, as well as from photometric data using TESS,
Spitzer
, and ground-based photometry from MuSCAT2, TRAPPIST-South, MONET-South, the George Mason University telescope, the Las Cumbres Observatory Global Telescope network, the El Sauce telescope, the TÜBİTAK National Observatory, the University of Louisville Manner Telescope, and WASP-South. We also present high-spatial resolution adaptive optics imaging with the Gemini Near-Infrared Imager. The low uncertainties in the mass and radius determination place LP 714-47 b among physically well-characterised planets, allowing for a meaningful comparison with planet structure models. The host star LP 714-47 is a slowly rotating early M dwarf (
T
eff
= 3950 ± 51 K) with a mass of 0.59 ± 0.02
M
⊙
and a radius of 0.58 ± 0.02
R
⊙
. From long-term photometric monitoring and spectroscopic activity indicators, we determine a stellar rotation period of about 33 d. The stellar activity is also manifested as correlated noise in the radial-velocity data. In the power spectrum of the radial-velocity data, we detect a second signal with a period of 16 days in addition to the four-day signal of the planet. This could be shown to be a harmonic of the stellar rotation period or the signal of a second planet. It may be possible to tell the difference once more TESS data and radial-velocity data are obtained.
The synthesis, by a sol-gel method, of organosilica-aluminum phosphates, (X)-AlPO(Y)-(Z), using three different silica precursors (X) 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane (C), ...3-(mercaptopropyl)trimethoxysilane (MPTMS) or Bis3-(triethoxysilyl)propyltetrasulfide (B), with varying Al/P molar ratio (Y = 3–10) and pH of the final gel (Z = 3–9), maintaining an Al/Si= 3 molar ratio, has been carried out. Materials were characterized by XRF, SEM-EDX, XRD, 1H–29Si CP, 27Al and 31P MAS NMR and nitrogen adsorption. The acidity of the solids was evaluated by TGA, XRF and XPS and their catalytic behavior in the etherification of glycerol with tert-butyl alcohol, under microwave irradiation. The solids with an Al/P molar ratio between 3 and 6, synthesized at a pH value over 3 with precursor C, exhibiting the highest values of acidity and predominantly a mesoporous character, showed the best catalytic behavior.
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•Synthesis parameters to obtain organosilica-aluminum phosphates by a sol-gel method were evaluated.•Aryl-sulfonic monosilane precursor gave rise to the highest silicon incorporation (92%).•Al/P ratio and the final pH strongly influence the acidity and textural properties.•Yield to di and tri-tertbutyl ethers of glycerol depends on both, acidity and mesoporosity.•A versatile procedure to obtain catalysts with different properties is described.
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•Iron phosphide based catalysts presenting different stoichiometry were prepared.•Fe2P phase is more active than FeP one in the HDO of phenol.•Cyclohexane and cyclohexene were the ...main products for all studied catalysts.•The presence of different iron phosphides in the catalysts was detrimental in the catalytic activity.•TOF is related to iron surface exposure, particle size and catalyst acidity.
Iron phosphide catalysts supported on silica with an iron loading of 15 wt% were synthesized and studied in the hydrodeoxygenation (HDO) of phenol. The amount of phosphorus varied in order to obtain iron phosphides with different stoichiometry. Catalysts containing Fe2P, FeP and FeP2 phases were obtained. The textural and structural properties of the prepared catalysts were evaluated by using different experimental techniques such as N2 adsorption-desorption at -196 °C, X-ray diffraction (XRD), Mössbauer spectroscopy, high resolution transmission spectroscopy (HRTEM), infrared spectroscopy (IR) of adsorbed CO at low temperature, X-ray photoelectron microscopy (XPS) and NH3 thermoprogrammed desorption (NH3-TPD). The catalytic activity was studied at 275 °C and at 15 and 5 bar of hydrogen pressure in the hydrodeoxygenation reaction of phenol. Characterization results evidenced that the initial P/Fe ratio employed in the synthesis not only governed the stoichiometry of the iron phosphide, but also the particle size, metallic surface exposure and acidity. The catalysts presenting unique phases were those presenting better activity in the HDO reaction of phenol. Moreover, Fe2P phase presented better results than FeP in terms of HDO conversion.
Background
The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma ...patients treated under the Spanish Expanded Access Program.
Methods
Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group.
Results
Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events.
Conclusion
Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases.
Summary
Background and Objective
The aim was assessing a short training for healthcare providers on patient‐focused counselling to treat childhood obesity in primary care, along with dietitian‐led ...workshops and educational materials.
Methods
Randomized clustered trial conducted with paediatrician‐nurse pairs (Basic Care Units BCU) in primary care centres from Tarragona (Spain). BCUs were randomized to intervention (MI) (motivational interview, dietitian‐led education, and educational materials) or control group (SC, standard care). Participants were 8–14‐year‐old children with obesity, undergoing 1–11 monthly treatment visits during 1 year at primary care centres. The primary outcome was BMI z‐score reduction.
Results
The study included 44 clusters (23 MI). Out of 303 allocated children, 201 (n = 106 MI) completed baseline, final visits, and at least one treatment visit and were included in the analysis. BMI z‐score reduction was −0.27 (±0.31) in SC, versus −0.36 (±0.35) in MI (p = 0.036).
Mixed models with centres as random effects showed greater reductions in BMI in MI than SC; differences were B = −0.11 (95% CI: −0.20, −0.01, p = 0.025) for BMI z‐score, and B = −2.06 (95% CI: −3.89, −0.23, p = 0.028) for BMI %. No severe adverse events related to the study were notified.
Conclusion
Training primary care professionals on motivational interviewing supported by dietitians and educational materials, enhanced the efficacy of childhood obesity therapy.
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