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Étienne Guyon nous a quittés en juillet dernier. Au cours de sa carrière, il a eu une diversité impressionnante d’activités liées aux sciences comme aux lettres, à la recherche comme à l’enseignement et à la diffusion scientifique.

Myotonic dystrophy type 1 (DM1) is a slowly progressive disease caused by abnormal CTG repetitions on the dystrophia myotonica protein kinase (DMPK) gene. Long mRNA from CTG repetitions stabilizes in nuclear foci and sequester muscleblind-like splicing regulator 1 (MBNL1). Cardinal signs of DM1 include muscle wasting and weakness. The impacts of DM1 progression on skeletal muscle are under-researched. Identifying physiopathological markers related to maximal strength loss over time in DM1. Twenty-two individuals with DM1 participated in two maximal isometric muscle strength (MIMS) evaluations of their knee extensors and two vastus lateralismuscle biopsies, 3 years apart. Muscle fiber typing, size (including minimal Feret’s diameter [MFD] and atrophy/hypertrophy factors [AF/HF]), and nuclear foci and MBNL1 colocalization (foci/MBNL1+) were evaluated. Immunoblotting was used to measure glycogen synthase kinase-3 beta (GSK3β), p62, LC3BI, LC3BII, and oxidative phosphorylation proteins. There are significant correlations between the fold changes of MIMS with type 1 fiber MFD (ρ= 0.483) and AF (ρ= –0.514). Regression analysis shows that baseline percentage of foci/MBNL1+ nuclei and strength training explain 44.1% of foci/MBNL1+ nuclei percentage variation over time. There are fair to excellent correlations between the fold changes of MIMS and GSK3β(ρ= 0.327), p62 (ρ= 0.473), LC3BI (ρ= 0.518), LC3BII (ρ= –0.391) and LC3BII/LC3BI (ρ= –0.773). Type 1 MFD decrease and AF increase are correlated with MIMS loss. There seems to be a plateau effect in foci/MBNL1+ nuclei accumulation and strength training helps decrease this accumulation. Autophagy marker LC3BII/LC3BI ratio has a good biomarker potential of MIMS loss, but more investigations are needed.

TMPRSS6 is a potential therapeutic target for the treatment of iron overload due to its role in regulating levels of hepcidin. Although potent TMPRSS6 inhibitors have been previously developed, their lack of specificity requires optimization to avoid potential side effects before pursuing preclinical development with in vivomodels. Here, using computer-aided drug design based on a TMPRSS6 homology model, we reveal that the S2 position of TMPRSS6 offers a potential avenue to achieve selectivity against other members of the TTSP family. Accordingly, we synthesized novel peptidomimetic molecules containing lipophilic amino acids at the P2 position to exploit this unexplored pocket. This enabled us to identify TMPRSS6-selective small molecules with low nanomolar affinity. Finally, pharmacokinetic parameters were determined, and a compound was found to be potent in cellulotoward its primary target while retaining TTSP-subtype selectivity and showing no signs of alteration in in vitroTEER experiments.

This work presents a study of the thermal sensitivity of p-n short silicon diodes represented by the temperature coefficient of current (TCC) for thermal sensing applications. It proposes an analytical model (AM) of the TCC of p-n short silicon diodes under low-level injections and in the temperature range of 300–400 K. First, the TCC is studied at diffusion and recombination regimes and it is discriminated between different physical contributions. Then, it is followed by a discussion on the origins and influences of these contributions to provide a usable and simplified analytical expression of the TCC. Finally, the proposed AM is compared to technology computer-aided design (TCAD) simulations and experimental results at 300–400 K. It shows a strong correlation for different designs of p-n short diodes.

ABSTRACTPurpose: Investigate acute locomotor, internal (heart rate (HR) and ratings of perceived exertion (RPE)) and neuromuscular responses to using wearable resistance loading for soccer-specific training. Methods: Twenty-six footballers from a French 5th division team completed a 9-week parallel-group training intervention (intervention group: n = 14, control: n = 12). The intervention group trained with wearable resistance (200-g on each posterior, distal-calf) for full-training sessions on Day + 2, D + 4 and unloaded on D + 5. Between-group differences in locomotor (GPS) and internal load were analyzed for full-training sessions and game simulation drills. Neuromuscular status was evaluated using pre- and post-training box-to-box runs. Data were analyzed using linear mixed-modelling, effect size ±90% confidence limits (ES ± 90%CL) and magnitude-based decisions. Results: Full-training sessions: Relative to the control, the wearable resistance group showed greater total distance (ES [lower, upper limits]: 0.25 [0.06, 0.44]), sprint distance (0.27 [0.08, 0.46]) and mechanical work (0.32 [0.13, 0.51]). Small game simulation (<190 m2/player): wearable resistance group showed small decreases in mechanical work (0.45 [0.14, 0.76]) and moderately lower average HR (0.68 [0.02, 1.34]). Large game simulation (>190 m2/player): no meaningful between-group differences were observed for all variables. Training induced small to moderate neuromuscular fatigue increases during post-training compared to pre-training box-to-box runs for both groups (Wearable resistance: 0.46 [0.31, 0.61], Control: 0.73 [0.53, 0.93]). Conclusion: For full training, wearable resistance induced higher locomotor responses, without affecting internal responses. Locomotor and internal outputs varied in response to game simulation size. Football-specific training with wearable resistance did not impact neuromuscular status differently than unloaded training.

AbstractRATIONALEAcute exacerbations of chronic obstructive pulmonary disease (AECOPD) accelerate decline in lung function and are associated with hospitalization. Patients with COPD are at risk for community acquired pneumonia (CAP). There may be a benefit to distinguish between these entities.OBJECTIVESThe objectives of this research were to assess differences in initial presentation and short-term lung function and symptom recovery in patients with COPD hospitalized for AECOPD or CAP.METHODSA single center, non-interventional, prospective cohort study of patients with COPD hospitalized with AECOPD or CAP was used. Baseline characteristics were collected. Spirometry was obtained on admission, at discharge, and 6-wk post-discharge. The primary outcome was change in forced expiratory volume in the first second (FEV1%) predicted over time. COPD Assessment Test (CAT) was used to assess symptom burden on admission and 6-wk post-discharge.MAIN RESULTSA total of 54 patients were recruited, all with at least moderate airflow obstruction. On admission, there were higher levels of CRP in COPD with CAP compared to AECOPD (86.4 [SD 81.9] vs 33.5 [35.4]). There was a statistically significant difference in FEV1% predicted (p = 0.0038) and CAT score (p = 0.0005) over time, after adjusting for presence of CAP. However, there was no difference in FEV1% predicted (p = 0.7184) or CAT score (p = 0.441), between those with an AECOPD and COPD with CAP, after adjusting for time. Average length of stay in hospital was longer in COPD with CAP than for AECOPD (11.0 [10.2] versus 6.9 [4.5] days).CONCLUSIONSTime is the principal factor in short term lung function and symptom recovery in patients with COPD hospitalized for acute respiratory decompensation.

Around the world, fire regimes are shifting due to changing climate, land use and management, and human populations and infrastructure. While fire is a healthy and necessary process for many ecosystems, altered fire regimes are increasing risk to both people and wildlife in many regions. Reducing risk requires a holistic approach with investment from many stakeholders. In this Voices, we ask: what aspects of fire hazard, vulnerability, and exposure can be mitigated, and what collaborations does this require?

AbstractObjective:To evaluate the impact of administering probiotics to prevent Clostridioides difficileinfection (CDI) among patients receiving therapeutic antibiotics.Design:Stepped-wedge cluster-randomized trial between September 1, 2016, and August 31, 2019.Setting:This study was conducted in 4 acute-care hospitals across an integrated health region.Patients:Hospitalized patients, aged ≥55 years.Methods:Patients were given 2 probiotic capsules daily (Bio-K+, Laval, Quebec, Canada), containing 50 billion colony-forming units of Lactobacillus acidophilusCL1285, L. caseiLBC80R, and L. rhamnosusCLR2. We measured hospital-acquired CDI (HA-CDI) and the number of positive C. difficiletests per 10,000 patient days as well as adherence to administration of Bio-K+ within 48 and 72 hours of antibiotic administration. Mixed-effects generalized linear models, adjusted for influenza admissions and facility characteristics, were used to evaluate the impact of the intervention on outcomes.Results:Overall adherence of Bio-K+ administration ranged from 76.9% to 84.6% when stratified by facility and periods. Rates of adherence to administration within 48 and 72 hours of antibiotic treatment were 60.2% –71.4% and 66.7%–75.8%, respectively. In the adjusted analysis, there was no change in HA-CDI (incidence rate ratio [IRR], 0.92; 95% confidence interval [CI], 0.68–1.23) or C. difficilepositivity rate (IRR, 1.05; 95% CI, 0.89–1.24). Discharged patients may not have received a complete course of Bio-K+. Our hospitals had a low baseline incidence of HA-CDI. Patients who did not receive Bio-K+ may have differential risks of acquiring CDI, introducing selection bias.Conclusions:Hospitals considering probiotics as a primary prevention strategy should consider the baseline incidence of HA-CDI in their population and timing of probiotics relative to the start of antimicrobial administration.

This review analyzes the published evidence regarding maternal factors that influence the developmental programming of long-term adiposity in humans and animals via the central nervous system (CNS). We describe the physiological outcomes of perinatal underfeeding and overfeeding and explore potential mechanisms that may mediate the impact of such exposures on the development of feeding circuits within the CNS—including the influences of metabolic hormones and epigenetic changes. The perinatal environment, reflective of maternal nutritional status, contributes to the programming of offspring adiposity. The in utero and early postnatal periods represent critically sensitive developmental windows during which the hormonal and metabolic milieu affects the maturation of the hypothalamus. Maternal hyperglycemia is associated with increased transfer of glucose to the fetus driving fetal hyperinsulinemia. Elevated fetal insulin causes increased adiposity and consequently higher fetal circulating leptin concentration. Mechanistic studies in animal models indicate important roles of leptin and insulin in central and peripheral programming of adiposity, and suggest that optimal concentrations of these hormones are critical during early life. Additionally, the environmental milieu during development may be conveyed to progeny through epigenetic marks and these can potentially be vertically transmitted to subsequent generations. Thus, nutritional and metabolic/endocrine signals during perinatal development can have lifelong (and possibly multigenerational) impacts on offspring body weight regulation.Graphical Abstract

Pitolisant hydrochloride is used to treat excessive daytime sleepiness in adults with narcolepsy. The drug is formulated as a crystalline solid, and a monoclinic P21form has been claimed in patents, but little additional information about the structure and polymorphism of the compound has been published. No new forms were obtained when we grew crystals from solution under various conditions. Re-examination of the crystals revealed a disordered and partially hydrated structure that resembles the one reported earlier but is not identical. Further insight was obtained by synthesizing analogues of pitolisant with its Cl substituent replaced by Me, F, and Br, followed by structural analysis of the hydrochloride salts by X-ray diffraction. Pitolisant hydrochloride and its three analogues showed very similar solid-state behavior, and each compound yielded new metastable forms when crystallized from melts. The lifetime of metastable form III of pitolisant hydrochloride could be extended significantly by adding small amounts of the fluoro analogue, but none of the metastable forms could be obtained as single crystals suitable for structural analysis. Computational predictions of the polymorphic landscapes of pitolisant hydrochloride and its analogues identified possible structures of the metastable forms. Dual experimental and computational approaches are already widely used in polymorphic screening, but our work shows the value of broadening these searches to include sets of structural analogues.

We report a whispering gallery mode resonator on a pillar using inkjet printing combined with traditional microfabrication techniques. This approach enables several different polymers on the same chip for sensing applications. However, polymers inherently exhibit sensitivity to multiple stimuli. To mitigate temperature sensitivity, careful selection of design parameters is crucial. By precisely tuning the undercut-to-radius ratio of the resonator, a linear dependence in temperature sensitivity ranging from −41.5 pm/°C to 23.4 pm/°C, with a zero-crossing point at 47.6% is achieved. Consequently, it is feasible to fabricate sensing devices based on undercut microdroplets with minimal temperature sensitivity. The lowest measured temperature sensitivity obtained was 5.9 pm/°C, for a resonator with an undercut-to-radius ratio of 53%.

Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery.

Single-cell proteomics by mass spectrometry (MS) allows the quantification of proteins with high specificity and sensitivity. To increase its throughput, we developed nano-proteomic sample preparation (nPOP), a method for parallel preparation of thousands of single cells in nanoliter-volume droplets deposited on glass slides. Here, we describe its protocol with emphasis on its flexibility to prepare samples for different multiplexed MS methods. An implementation using the plexDIA MS multiplexing method, which uses non-isobaric mass tags to barcode peptides from different samples for data-independent acquisition, demonstrates accurate quantification of ~3,000–3,700 proteins per human cell. A separate implementation with isobaric mass tags and prioritized data acquisition demonstrates analysis of 1,827 single cells at a rate of >1,000 single cells per day at a depth of 800–1,200 proteins per human cell. The protocol is implemented by using a cell-dispensing and liquid-handling robot—the CellenONE instrument—and uses readily available consumables, which should facilitate broad adoption. nPOP can be applied to all samples that can be processed to a single-cell suspension. It takes 1 or 2 d to prepare >3,000 single cells. We provide metrics and software (the QuantQC R package) for quality control and data exploration. QuantQC supports the robust scaling of nPOP to higher plex reagents for achieving reliable and scalable single-cell proteomics.

Memristors allow computing in memory, which may be leveraged by deep neural network (DNN) accelerators to reduce energy footprint. However, such gains in energy efficiency come at the cost of noise on the computation results due to the analog nature of memristors. In this work, we introduce a theoretical framework to estimate the mean squared error (MSE) of a memristor-based DNN. We propose an efficient software implementation of this framework which is shown to be orders of magnitude faster than using Monte-Carlo simulations. Additionally, we study two different techniques for mapping convolutional layers to memristors and compare their relative impact on the mean squared error and its computation time. The accuracy of the proposed analysis is first evaluated on a simple regression problem, and then on a more complex classification task with a network capable of achieving high accuracy on the CIFAR-10 dataset, which shows that our method is efficient over practical up-to-date DNNs. The proposed framework is then used to perform a meta-heuristic optimization of the memristor maximal conductance value so as to minimize the energy usage.11The code for the framework presented in this work is available at https://github.com/sebastienwood/MemSE

BackgroundHome mechanical ventilation (HMV) is the treatment for chronic hypercapnic alveolar hypoventilation. The proportion and evolution of paediatric invasive (IMV) and non-invasive (NIV) HMV across the world is unknown, as well as the disorders and age of children using HMV.MethodsSearch of Medline/PubMed for publications of paediatric surveys on HMV from 2000 to 2023.ResultsData from 32 international reports, representing 8815 children (59% boys) using HMV, were analysed. A substantial number of children had neuromuscular disorders (NMD; 37%), followed by cardiorespiratory (Cardio-Resp; 16%), central nervous system (CNS; 16%), upper airway (UA; 13%), other disorders (Others; 10%), central hypoventilation (4%), thoracic (3%) and genetic/congenital disorders (Gen/Cong; 1%). Mean age±SD (range) at HMV initiation was 6.7±3.7 (0.5–14.7) years. Age distribution was bimodal, with two peaks around 1–2 and 14–15 years. The number and proportion of children using NIV was significantly greater than that of children using IMV (n=6362 vs 2453, p=0.03; 72% vs 28%, p=0.048), with wide variations among countries, studies and disorders. NIV was used preferentially in the preponderance of children affected by UA, Gen/Cong, Thoracic, NMD and Cardio-Resp disorders. Children with NMD still receiving primary invasive HMV were mainly type I spinal muscular atrophy (SMA). Mean age±SD at initiation of IMV and NIV was 3.3±3.3 and 8.2±4.4 years (p<0.01), respectively. The rate of children receiving additional daytime HMV was higher with IMV as compared with NIV (69% vs 10%, p<0.001). The evolution of paediatric HMV over the last two decades consists of a growing number of children using HMV, in parallel to an increasing use of NIV in recent years (2020–2023). There is no clear trend in the profile of children over time (age at HMV). However, an increasing number of patients requiring HMV were observed in the Gen/Cong, CNS and Others groups. Finally, the estimated prevalence of paediatric HMV was calculated at 7.4/100 000 children.ConclusionsPatients with NMD represent the largest group of children using HMV. NIV is increasingly favoured in recent years, but IMV is still a prevalent intervention in young children, particularly in countries indicating less experience with NIV.

Abstract: The use of ketamine in conjunction with morphine to reduce postoperative pain has been explored in several different surgery subtypes with conflicting results. Ketamine has shown promise to have both opioid sparing and analgesic effects in the postoperative setting. This study aimed to elucidate ketamine’s ability to reduce morphine equivalent consumption and improve patient satisfaction after spinal fusion surgery for the correction of idiopathic scoliosis. This surgery is known to be associated with significant postoperative pain which impedes the ability to improve patient satisfaction, and may complicate the recovery timeline. Currently, the standard therapeutic regimen consists of patient-controlled analgesia morphine and the use of other opioids such as hydromorphone. A prospective, randomized double-blinded, placebo-controlled trial was performed to compare the standard morphine equivalent therapy alone against a standard therapy in conjunction with ketamine. Fifty adolescent patients were enrolled and randomized. Results yielded a significant reduction in postoperative morphine equivalent consumption (p= 0.042), adjusted postoperative pain scores (p&lt; 0.001), and incidence of nausea and vomiting (p= 0.045). The application of ketamine as an analgesic in conjunction with the current standard of morphine equivalent therapy may serve as a superior pain control regimen for spinal surgeries in young population. This regimen enhancement may be generalizable to other surgery subtypes within similar populations. Level of evidence: Level I.

Airway hillocks are stratified epithelial structures of unknown function1. Hillocks persist for months and have a unique population of basal stem cells that express genes associated with barrier function and cell adhesion. Hillock basal stem cells continually replenish overlying squamous barrier cells. They exhibit dramatically higher turnover than the abundant, largely quiescent classic pseudostratified airway epithelium. Hillocks resist a remarkably broad spectrum of injuries, including toxins, infection, acid and physical injury because hillock squamous cells shield underlying hillock basal stem cells from injury. Hillock basal stem cells are capable of massive clonal expansion that is sufficient to resurface denuded airway, and eventually regenerate normal airway epithelium with each of its six component cell types. Hillock basal stem cells preferentially stratify and keratinize in the setting of retinoic acid signalling inhibition, a known cause of squamous metaplasia2,3. Here we show that mouse hillock expansion is the cause of vitamin A deficiency-induced squamous metaplasia. Finally, we identify human hillocks whose basal stem cells generate functional squamous barrier structures in culture. The existence of hillocks reframes our understanding of airway epithelial regeneration. Furthermore, we show that hillocks are one origin of ‘squamous metaplasia’, which is long thought to be a precursor of lung cancer.

Major depressive disorder (MDD) is the leading cause of disability worldwide. Of individuals with MDD, 30% to 50% are unresponsive to common antidepressants, highlighting untapped causal biological mechanisms. Dysfunction in the microbiota-gut-brain axis has been implicated in MDD pathogenesis. Exposure to chronic stress disrupts blood-brain barrier integrity; still, little is known about intestinal barrier function in these conditions, particularly for the small intestine, where absorption of most foods and drugs takes place.

RationaleEndoscopic lung volume reduction improves lung function, quality of life and exercise capacity in severe emphysema patients. However, its effect on the diaphragm function is not well understood. We hypothesised that endoscopic lung volume reduction increases its strength by modifying its shape.ObjectivesTo investigate changes in both diaphragm shape and strength induced by the insertion of endobronchial valves.MethodsIn 19 patients, both the diaphragm shape and strength were investigated respectively by 3D Slicer software applied on CT scans acquired at functional residual capacity and by transdiaphragmatic pressure measurements by bilateral magnetic stimulation of the phrenic nerves before and 3 months after unilateral valves insertion.Measurements and main resultsAfter lung volume reduction (median (IQR), 434 mL (−597 to −156], p<0.0001), diaphragm strength increased (transdiaphragmatic pressure: 3 cmH2O (2.3 to 4.2), p<0.0001). On the treated side, this increase was associated with an increase in the coronal (16 mm (13 to 24), p<0.0001) and sagittal (26 mm (21 to 30), p<0.0001) lengths as well as in the area of the zone of apposition (62 cm2(3 to 100), p<0.0001) with a decrease in the coronal (8 mm (−12 to −4), p<0.0001) and sagittal (9 mm (−18 to −2), p=0.0029) radii of curvature.ConclusionsEndoscopic lung volume reduction modifies the diaphragm shape by increasing its length and its zone of apposition and by decreasing its radius of curvature on the treated side, resulting in an increase in its strength.Trial registration numberNCT05799352.

ABSTRACTSkeletal muscles play key roles in movement, posture, thermogenesis, and whole-body metabolism. Autophagy plays essential roles in the regulation of muscle mass, function and integrity. However, the molecular machinery that regulates autophagy is still incompletely understood. In our recent study, we identified and characterized a novel Forkhead Box O (FoxO)-dependent gene, PHAF1/MYTHO (phagophore assembly factor 1/macro-autophagy and youth optimizer), as a novel autophagy regulator that controls muscle integrity. MYTHO/PHAF1 is upregulated in multiple conditions leading to muscle atrophy, and downregulation of its expression spares muscle atrophy triggered by fasting, denervation, cachexia and sepsis. Overexpression of PHAF1/MYTHO is sufficient to induce muscle atrophy. Prolonged downregulation of PHAF1/MYTHO causes a severe myopathic phenotype, which is characterized by impaired autophagy, muscle weakness, myofiber degeneration, mammalian target of rapamycin complex 1 (mTORC1) hyperactivation and extensive ultrastructural defects, such as accumulation of proteinaceous and membranous structures and tubular aggregates. This myopathic phenotype is attenuated upon administration of the mTORC1 inhibitor rapamycin. These findings position PHAF1/MYTHO as a novel regulator of skeletal muscle autophagy and tissue integrity.

Purpose: Public safety (communicators; e.g. 9-1-1, police, fire and ambulance call-takers and dispatchers), like many other public safety personnel (e.g. police, paramedics), (re)suffer operational stress injuries (OSIs) that are too often hidden and at a prevalence higher than the general population. Unfortunately, there are very little data for OSI rates in Canadian communicators. To the authors’ knowledge, this is the only pan-Canadian study focusing on organizational culture, and its potential influence on OSIs, within the communicator context. Design/methodology/approach: The authors conducted a 179-item online survey of Canadian communicators comprising 17 validated screenings for occupational stress injuries and symptoms and four open-ended questions relating to their agency's organizational culture. The authors thematically analysed participants' open-ended responses and their screening scores. Findings: A semi-grounded thematic approach revealed that managers and supervisors were significant contributors to negative perceptions (n= 165) of organizational culture, potentially resulting in or worsening existing OSIs. Specifically, leadership was viewed as ineffective, inconsistent, unsupportive, abusive and toxic, with limited understanding of communicator roles. Communicators described feeling devalued, particularly when leaders fail to recognize communicator OSIs, which can perpetuate stigma. Conversely, positive leaders (n= 24) were described as supportive, communicative and encouraging. Originality/value: The findings suggest that while leadership behaviours are a key factor in employee well-being, it varies considerably across agencies, impacting treatment-seeking behaviours. The authors’ new understandings of leaders' roles in OSIs may help reduce the frequency and severity of communicator OSIs, helping ensure that emergency services are delivered to Canadians.

Due in part to climate change, wildfire activity is increasing, with the potential for greater public health impact from smoke in downwind communities. Studies examining the health effects of wildfire smoke have focused primarily on fine particulate matter (PM2.5), but there is a need to better characterize other constituents, such as hazardous air pollutants (HAPs). HAPs are chemicals known or suspected to cause cancer or other serious health effects that are regulated by the United States (US) Environmental Protection Agency. Here, we analyzed concentrations of 21 HAPs in wildfire smoke from 2006 to 2020 at 309 monitors across the western US. Additionally, we examined HAP concentrations measured in a major population center (San Jose, CA) affected by multiple fires from 2017 to 2020. We found that concentrations of select HAPs, namely acetaldehyde, acrolein, chloroform, formaldehyde, manganese, and tetrachloroethylene, were all significantly elevated on smoke-impacted versus nonsmoke days (P< 0.05). The largest median increase on smoke-impacted days was observed for formaldehyde, 1.3 μg/m3(43%) higher than that on nonsmoke days. Acetaldehyde increased 0.73 μg/m3(36%), and acrolein increased 0.14 μg/m3(34%). By better characterizing these chemicals in wildfire smoke, we anticipate that this research will aid efforts to reduce exposures in downwind communities.

Sustainable water management should consider climate change effects to ensure its future availability. Hydrological modeling is a supportive tool for this analysis, which has been used in this work to assess the climate change impacts on the water resources of three basins under Mediterranean climate (Ompólveda and Salado River basins, in Spain, and Guadalupe River basin, in Mexico).

Skeletal muscle regeneration relies on the tightly temporally regulated lineage progression of muscle stem/progenitor cells (MPCs) from activation to proliferation and, finally, differentiation. However, with aging, MPC lineage progression is disrupted and delayed, ultimately causing impaired muscle regeneration. Extracellular vesicles (EVs) have attracted broad attention as next-generation therapeutics for promoting tissue regeneration. As a next step toward clinical translation, strategies to manipulate EV effects on downstream cellular targets are needed. Here, we developed an engineering strategy to tune the therapeutic potential of EVs using nanotopographical cues. We found that EVs released by young MPCs cultured on flat substrates (fEVs) promoted the proliferation of aged MPCs while EVs released by MPCs cultured on nanogratings (nEVs) promoted myogenic differentiation. We then employed a bioengineered 3D muscle aging model to optimize the administration protocol and test the therapeutic potential of fEVs and nEVs in a high-throughput manner. We found that the sequential administration first of fEVs during the phase of MPC proliferative expansion (i.e., 1 day after injury) followed by nEV administration at the stage of MPC differentiation (i.e., 3 days after injury) enhanced aged muscle regeneration to a significantly greater extent than fEVs and nEVs delivered either in isolation or mixed. The beneficial effects of the sequential EV treatment strategy were further validated in vivo, as evidenced by increased myofiber size and improved functional recovery. Collectively, our study demonstrates the ability of topographical cues to tune EV therapeutic potential and highlights the importance of optimizing the EV administration strategy to accelerate aged skeletal muscle regeneration.

Wildfires have increased in frequency and area burned, trends expected to continue with climate change. Among other effects, fires release pollutants into the atmosphere, representing a risk to human health and downwind terrestrial and aquatic ecosystems. While human health risks are well studied, the ecological impacts to downwind ecosystems are not, and this gap may present a constraint on developing an adequate assessment of the ecological risks associated with downwind wildfire exposure. Here, we first screened the scientific literature to assess general knowledge about pathways and end points of a conceptual model linking wildfire generated pollutants and other materials to downwind ecosystems. We found a substantial body of literature on the composition of wildfire derived pollution and materials in the atmosphere and subsequent transport, yet little observational or experimental work on their effects on downwind ecological end points. This dearth of information raises many questions related to adequately assessing the ecological risk of downwind exposure, especially given increasing wildfire trends. To guide future research, we pose eight questions within the well-established US EPA ecological risk assessment paradigm that if answered would greatly improve ecological risk assessment and, ultimately, management strategies needed to reduce potential wildfire impacts.

Mass spectrometry (MS) enables specific and accurate quantification of proteins with ever-increasing throughput and sensitivity. Maximizing this potential of MS requires optimizing data acquisition parameters and performing efficient quality control for large datasets. To facilitate these objectives for data-independent acquisition (DIA), we developed a second version of our framework for data-driven optimization of MS methods (DO-MS). The DO-MS app v2.0 (do-ms.slavovlab.net) allows one to optimize and evaluate results from both label-free and multiplexed DIA (plexDIA) and supports optimizations particularly relevant to single-cell proteomics. We demonstrate multiple use cases, including optimization of duty cycle methods, peptide separation, number of survey scans per duty cycle, and quality control of single-cell plexDIA data. DO-MS allows for interactive data display and generation of extensive reports, including publication of quality figures that can be easily shared. The source code is available at github.com/SlavovLab/DO-MS.

L’entretien présenté ici est destiné à prendre la suite du « dossier photovoltaïque » publié en 2007 dans les numéros 5 et 6 de Reflets de la physique. Le contexte a beaucoup évolué depuis quinze ans, tant du point de vue de la recherche que de l’économie et de l’acceptation par la société.