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In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression.

There have been 77 TNOs discovered to be librating in the distant trans-Neptunian resonances (beyond the 2:1 resonance, at semimajor axes greater than 47.7 au) in four well-characterized surveys: the Outer Solar System Origins Survey (OSSOS) and three similar prior surveys. Here, we use the OSSOS Survey Simulator to measure their intrinsic orbital distributions using an empirical parameterized model. Because many of the resonances had only one or very few detections, j:k resonant objects were grouped by k in order to have a better basis for comparison between models and reality. We also use the Survey Simulator to constrain their absolute populations, finding that they are much larger than predicted by any published Neptune migration model to date; we also find population ratios that are inconsistent with published models, presenting a challenge for future Kuiper Belt emplacement models. The estimated population ratios between these resonances are largely consistent with scattering–sticking predictions, though further discoveries of resonant TNOs with high-precision orbits will be needed to determine whether scattering–sticking can explain the entire distant resonant population or not.

Measuring the abundances of carbon and oxygen in exoplanet atmospheres is considered a crucial avenue for unlocking the formation and evolution of exoplanetary systems 1 , 2 . Access to the chemical inventory of an exoplanet requires high-precision observations, often inferred from individual molecular detections with low-resolution space-based 3 – 5 and high-resolution ground-based 6 – 8 facilities. Here we report the medium-resolution ( R  ≈ 600) transmission spectrum of an exoplanet atmosphere between 3 and 5 μm covering several absorption features for the Saturn-mass exoplanet WASP-39b (ref.  9 ), obtained with the Near Infrared Spectrograph (NIRSpec) G395H grating of JWST. Our observations achieve 1.46 times photon precision, providing an average transit depth uncertainty of 221 ppm per spectroscopic bin, and present minimal impacts from systematic effects. We detect significant absorption from CO 2 (28.5 σ ) and H 2 O (21.5 σ ), and identify SO 2 as the source of absorption at 4.1 μm (4.8 σ ). Best-fit atmospheric models range between 3 and 10 times solar metallicity, with sub-solar to solar C/O ratios. These results, including the detection of SO 2 , underscore the importance of characterizing the chemistry in exoplanet atmospheres and showcase NIRSpec G395H as an excellent mode for time-series observations over this critical wavelength range 10 . The medium-resolution transmission spectrum of the exoplanet WASP-39b, described using observations from the Near Infrared Spectrograph G395H grating aboard JWST, shows significant absorption from CO 2 and H 2 O and detection of SO 2 .

Carbon monoxide was recently reported in the atmosphere of the hot Jupiter WASP-39b using the NIRSpec PRISM transit observation of this planet, collected as part of the JWST Transiting Exoplanet Community Early Release Science Program. This detection, however, could not be confidently confirmed in the initial analysis of the higher-resolution observations with NIRSpec G395H disperser. Here we confirm the detection of CO in the atmosphere of WASP-39b using the NIRSpec G395H data and cross-correlation techniques. We do this by searching for the CO signal in the unbinned transmission spectrum of the planet between 4.6 and 5.0 μm, where the contribution of CO is expected to be higher than that of other anticipated molecules in the planet’s atmosphere. Our search results in a detection of CO with a cross-correlation function (CCF) significance of 6.6σ when using a template with only 12C16O lines. The CCF significance of the CO signal increases to 7.5σ when including in the template lines from additional CO isotopologues, with the largest contribution being from 13C16O. Our results highlight how cross-correlation techniques can be a powerful tool for unveiling the chemical composition of exoplanetary atmospheres from medium-resolution transmission spectra, including the detection of isotopologues.

Aims Women who had gestational diabetes mellitus (GDM) have a high risk of type 2 diabetes mellitus (T2DM) in the years following pregnancy. Most follow-up screening studies have been conducted in limited geographical areas leading to large variability in the results. The aim of our investigation was to measure how the publication of guidelines affected early screening for T2DM after a pregnancy with GDM during the period 2007–2013, in France. Methods We conducted a retrospective cohort study in a representative sample of 1/97th of the French population using data from the “National Health Insurance Inter-Regime Information System,” which collects individual hospital and non-hospital data for healthcare consumption. Results The sample included 49,080 women who gave birth in 2007–2013. In the following 3 months, only 18.49% of women with GDM had an oral glucose tolerance test or a blood glucose test in 2007. This rate had not significantly increased in 2013 ( p  = 0.18). The proportion of women with GDM who had the recommended glycemic follow-up at 3 months (20.30 vs. 21.58%, p  = 0.19) and 6 months (32.48 vs. 37.16%, p  = 0.08) was not significantly different before the guidelines (2008–2009) and after the guidelines (2012–2013). At 12 months, the difference was significant (46.77 vs. 54.05%, p  = 0.009). Conclusion Postpartum screening has improved only slightly since the guidelines and remains largely insufficient, with less than 25% of women with GDM screened in the first 3 months. In the first year after delivery, less than 60% of women were screened for T2DM.

Curcumin, a major active component of turmeric ( Curcuma longa , L.), has anticancer effects. In vitro studies suggest that curcumin inhibits cancer cell growth by activating apoptosis, but the mechanism underlying these effects is still unclear. Here, we investigated the mechanisms leading to apoptosis in curcumin-treated cells. Curcumin induced endoplasmic reticulum stress causing calcium release, with a destabilization of the mitochondrial compartment resulting in apoptosis. These events were also associated with lysosomal membrane permeabilization and of caspase-8 activation, mediated by cathepsins and calpains, leading to Bid cleavage. Truncated tBid disrupts mitochondrial homeostasis and enhance apoptosis. We followed the induction of autophagy, marked by the formation of autophagosomes, by staining with acridine orange in cells exposed curcumin. At this concentration, only the early events of apoptosis (initial mitochondrial destabilization with any other manifestations) were detectable. Western blotting demonstrated the conversion of LC3-I to LC3-II (light chain 3), a marker of active autophagosome formation. We also found that the production of reactive oxygen species and formation of autophagosomes following curcumin treatment was almost completely blocked by N -acetylcystein, the mitochondrial specific antioxidants MitoQ10 and SKQ1, the calcium chelators, EGTA-AM or BAPTA-AM, and the mitochondrial calcium uniporter inhibitor, ruthenium red. Curcumin-induced autophagy failed to rescue all cells and most cells underwent type II cell death following the initial autophagic processes. All together, these data imply a fail-secure mechanism regulated by autophagy in the action of curcumin, suggesting a therapeutic potential for curcumin. Offering a novel and effective strategy for the treatment of malignant cells.

Observing exoplanets through transmission spectroscopy supplies detailed information about their atmospheric composition, physics and chemistry. Before the James Webb Space Telescope (JWST), these observations were limited to a narrow wavelength range across the near-ultraviolet to near-infrared, alongside broadband photometry at longer wavelengths. To understand more complex properties of exoplanet atmospheres, improved wavelength coverage and resolution are necessary to robustly quantify the influence of a broader range of absorbing molecular species. Here we present a combined analysis of JWST transmission spectroscopy across four different instrumental modes spanning 0.5–5.2 μm using Early Release Science observations of the Saturn-mass exoplanet WASP-39 b. Our uniform analysis constrains the orbital and stellar parameters within subpercentage precision, including matching the precision obtained by the most precise asteroseismology measurements of stellar density to date, and it further confirms the presence of Na, K, H 2 O, CO, CO 2 and SO 2 as atmospheric absorbers. Through this process, we have improved the agreement between the transmission spectra of all modes, except for the NIRSpec PRISM, which is affected by partial saturation of the detector. This work provides strong evidence that uniform light curve analysis is an important aspect to ensuring reliability when comparing the high-precision transmission spectra provided by JWST. A combined analysis of datasets across four JWST instrument modes provides a benchmark transmission spectrum for the Saturn-mass WASP-39 b. The broad wavelength range and high resolution constrain orbital and stellar parameters to below 1%.

The study of binary Kuiper Belt objects helps to probe the dynamic conditions present during planet formation in the solar system. We report on the mutual-orbit determination of 2001 QW322, a Kuiper Belt binary with a very large separation whose properties challenge binary-formation and -evolution theories. Six years of tracking indicate that the binary's mutual-orbit period is approximately 25 to 30 years, that the orbit pole is retrograde and inclined 50 degrees to 62 degrees from the ecliptic plane, and, most surprisingly, that the mutual orbital eccentricity is <0.4. The semimajor axis of 105,000 to 135,000 kilometers is 10 times that of other near-equal-mass binaries. Because this weakly bound binary is prone to orbital disruption by interlopers, its lifetime in its present state is probably less than 1 billion years.

AimProtein–energy malnutrition is known to be involved in wound healing. While wound healing in patients with diabetic foot ulcers (DFU) is a complex and multifactorial process, the role of malnutrition in this case has rarely been explored. The objective of this study was to determine whether the nutritional status of diabetic patients influences the healing of DFU.Methods48 patients were included in this prospective, single-center study. All patients with comorbidities or factors involving malnutrition or influencing biological measurements were excluded. Patients were followed up for 24 weeks.ResultsThe malnutrition rate was 29.2% at baseline and 25.6% at the end of the study. The difference was not significant. Of the 35 patients with wound healing, 29% were undernourished at inclusion and 17% at the end of the study. Of the 12 patients without wound healing, 50% were undernourished at inclusion, and 42% at the end of the study. These differences were not significant. Rate and speed of wound healing were not associated with malnutrition at inclusion. 15% of patients without malnutrition at baseline had final malnutrition.ConclusionWe demonstrated that wound healing was not affected by the initial presence of malnutrition. In our study, there is no evidence to support nutritional intervention to improve wound healing in diabetic patients. Nevertheless, malnutrition is responsible for an increase in morbidity and mortality and it is essential to identify malnutrition systematically for all patients with DFU, initially and during follow-up to treat it quickly and efficiently.

AimThe impact of cholesteryl ester transfer protein (CETP) on atherosclerotic development in humans remains unclear. Plasma cholesteryl ester transfer was shown to be associated with carotid intima-media thickness in type 2 diabetic (T2D) patients with adequate metabolic control. Since glycation of CETP may influence cholesteryl ester transfer processes, it is important to determine if plasma cholesteryl ester transfer is still a determinant of carotid intima-media thickness (IMT) in patients with poorly controlled diabetes. The aim of the present study was to determine whether CETP activity influences carotid IMT in T2D patients with poor metabolic control.MethodsIn 110 individuals with T2D, we measured CETP mass concentration with ELISA, CETP activity with a radioactivity method and carotid intima-media thickness with high-resolution real-time B-mode ultrasonography.ResultsThe mean HbA1C was 8.8 ± 1.7%. Carotid IMT did not correlate with CETP activity in the total population. In T2D patients with HbA1C < 8% (n = 33), mean HbA1C was 6.9% and the correlation between carotid IMT and CETP activity was not significant (p = 0.09). In a multivariable analysis that included the total population, carotid intima-media thickness was positively associated with diabetes duration (p = 0.02) but not with CETP activity or HbA1C.ConclusionsWe observed no correlation between carotid intima-media thickness, a marker of early atherosclerosis, and CETP activity in T2D patients with poor metabolic control. Disease duration, which reflects accumulated metabolic abnormalities, may have blunted the potential effect of CETP on atherosclerosis. Metabolic control appears essential to determine the pro- or anti-atherogenic influence of CETP in patients with T2D.