The rise of inorganic–biological hybrid organisms for solar-to-chemical production has spurred mechanistic investigations into the dynamics of the biotic–abiotic interface to drive the development of ...next-generation systems. The model system, Moorella thermoacetica– cadmium sulfide (CdS), combines an inorganic semiconductor nanoparticle light harvester with an acetogenic bacterium to drive the photosynthetic reduction of CO₂ to acetic acid with high efficiency. In this work, we report insights into this unique electrotrophic behavior and propose a charge-transfer mechanism from CdS to M. thermoacetica. Transient absorption (TA) spectroscopy revealed that photoexcited electron transfer rates increase with increasing hydrogenase (H₂ase) enzyme activity. On the same time scale as the TA spectroscopy, time-resolved infrared (TRIR) spectroscopy showed spectral changes in the 1,700–1,900-cm−1 spectral region. The quantum efficiency of this system for photosynthetic acetic acid generation also increased with increasing H₂ase activity and shorter carrier lifetimes when averaged over the first 24 h of photosynthesis. However, within the initial 3 h of photosynthesis, the rate followed an opposite trend: The bacteria with the lowest H₂ase activity photosynthesized acetic acid the fastest. These results suggest a two-pathway mechanism: a high quantum efficiency charge-transfer pathway to H₂ase generating H₂ as a molecular intermediate that dominates at long time scales (24 h), and a direct energy-transducing enzymatic pathway responsible for acetic acid production at short time scales (3 h). This work represents a promising platform to utilize conventional spectroscopic methodology to extract insights from more complex biotic–abiotic hybrid systems.
Key points
Muscle infiltration with adipose tissue (IMAT) is common and associated with loss of skeletal muscle strength and physical function across a diverse set of pathologies.
Whether the ...association between IMAT and muscle weakness is causative or simply correlative remains an open question that needs to be addressed to effectively guide muscle strengthening interventions in people with increased IMAT.
In the present studies, we demonstrate that IMAT deposition causes decreased muscle strength using mouse models.
These findings indicate IMAT is a novel therapeutic target for muscle dysfunction.
Intramuscular adipose tissue (IMAT) is associated with deficits in strength and physical function across a wide array of conditions, from injury to ageing to metabolic disease. Due to the diverse aetiologies of the primary disorders involving IMAT and the strength of the associations, it has long been proposed that IMAT directly contributes to this muscle dysfunction. However, infiltration of IMAT and reduced strength could both be driven by muscle disuse, injury and systemic disease, making IMAT simply an ‘innocent bystander.’ Here, we utilize novel mouse models to evaluate the direct effect of IMAT on muscle contraction. First, we utilize intramuscular glycerol injection in wild‐type mice to evaluate IMAT in the absence of systemic disease. In this model we find that, in isolation from the neuromuscular and circulatory systems, there remains a muscle‐intrinsic association between increased IMAT volume and decreased contractile tension (r2 > 0.5, P < 0.01) that cannot be explained by reduction in contractile material. Second, we utilize a lipodystrophic mouse model which cannot generate adipocytes to ‘rescue’ the deficits. We demonstrate that without IMAT infiltration, glycerol treatment does not reduce contractile force (P > 0.8). Taken together, this indicates that IMAT is not an inert feature of muscle pathology but rather has a direct impact on muscle contraction. This finding suggests that novel strategies targeting IMAT may improve muscle strength and function in a number of populations.
Key points
Muscle infiltration with adipose tissue (IMAT) is common and associated with loss of skeletal muscle strength and physical function across a diverse set of pathologies.
Whether the association between IMAT and muscle weakness is causative or simply correlative remains an open question that needs to be addressed to effectively guide muscle strengthening interventions in people with increased IMAT.
In the present studies, we demonstrate that IMAT deposition causes decreased muscle strength using mouse models.
These findings indicate IMAT is a novel therapeutic target for muscle dysfunction.
•GR primary target (GRPT) Pik3r1 mediates GC-induced atrophy and insulin resistance in myotubes.•GRPT Cblb, Pid1, Ddit4, Sesn1, Klf15 and Mknk2 suppress the insulin/IGF1-mTOR signaling.•GRPT FoxO3 ...and MuRF1 with GC-induced FoxO1 and MAFbx promote protein degradation.•GRPT C/EBPβ with GC-induced p300 & C/EBPδ activate the transcription of myostatin to inhibit Akt.
Glucocorticoids (GCs) exert key metabolic influences on skeletal muscle. GCs increase protein degradation and decrease protein synthesis. The released amino acids are mobilized from skeletal muscle to liver, where they serve as substrates for hepatic gluconeogenesis. This metabolic response is critical for mammals’ survival under stressful conditions, such as fasting and starvation. GCs suppress insulin-stimulated glucose uptake and utilization and glycogen synthesis, and play a permissive role for catecholamine-induced glycogenolysis, thus preserving the level of circulating glucose, the major energy source for the brain. However, chronic or excess exposure of GCs can induce muscle atrophy and insulin resistance. GCs convey their signal mainly through the intracellular glucocorticoid receptor (GR). While GR can act through different mechanisms, one of its major actions is to regulate the transcription of its primary target genes through genomic glucocorticoid response elements (GREs) by directly binding to DNA or tethering onto other DNA-binding transcription factors. These GR primary targets trigger physiological and pathological responses of GCs. Much progress has been made to understand how GCs regulate protein and glucose metabolism. In this review, we will discuss how GR primary target genes confer metabolic functions of GCs, and the mechanisms governing the transcriptional regulation of these targets. Comprehending these processes not only contributes to the fundamental understanding of mammalian physiology, but also will provide invaluable insight for improved GC therapeutics.
Array programming with NumPy Harris, Charles R; Millman, K Jarrod; van der Walt, Stéfan J ...
Nature,
09/2020, Volume:
585, Issue:
7825
Journal Article
Peer reviewed
Open access
Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array ...programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves
and in the first imaging of a black hole
. Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis.
Tissue-resident macrophages require specific milieus for the maintenance of defining gene-expression programs. Expression of the transcription factor GATA6 is required for the homeostasis, function ...and localization of peritoneal cavity-resident macrophages. Gata6 expression is maintained in a non-cell autonomous manner and is elicited by the vitamin A metabolite, retinoic acid. Here, we found that the GATA6 transcriptional program is a common feature of macrophages residing in all visceral body cavities. Retinoic acid-dependent and -independent hallmark genes of GATA6+ macrophages were induced by mesothelial and fibroblastic stromal cells that express the transcription factor Wilms’ Tumor 1 (WT1), which drives the expression of two rate-limiting enzymes in retinol metabolism. Depletion of Wt1+ stromal cells reduced the frequency of GATA6+ macrophages in the peritoneal, pleural and pericardial cavities. Thus, Wt1+ mesothelial and fibroblastic stromal cells constitute essential niche components supporting the tissue-specifying transcriptional landscape and homeostasis of cavity-resident macrophages.
Display omitted
•Large cavity macrophages (LCMs) reside in peritoneal, pleural, and pericardial spaces•LCMs express the retinoic-acid-responsive transcription factor GATA6•Wt1+ stromal cells generate retinoic acid and maintain LCM GATA6 expression•Genetic ablation of Wt1+ stroma elicits loss of LCM across cavity spaces
Buechler et al. show that large cavity macrophages (LCMs), which rely on the retinoic-acid-responsive transcription factor GATA6, are found in all visceral cavity spaces. Wt1+ mesothelial and fibroblastic stromal cells maintain the LCM transcriptome in part via the generation of retinoic acid and are required for LCM homeostasis in vivo.
Exogenous glucocorticoid administration results in hyperglycemia, insulin resistance, hepatic dyslipidemia, and hypertension, a constellation of findings known as Cushing's syndrome. These effects ...are mediated by the glucocorticoid receptor (GR). Because GR activation in liver and adipose has been implicated in metabolic syndrome (MS), we wanted to determine the role of GR in these tissues in the development of MS. Because GR knockout (KO) mice (whole-body KO) exhibit perinatal lethality due to respiratory failure, we generated tissue-specific (liver or adipose) GRKO mice using cre-lox technology. Real-time PCR analysis of liver mRNA from dexamethasone-treated wildtype (WT) and liver GRKO mice indicated that hepatic GR regulates the expression of key genes involved in gluconeogenesis and glycogen metabolism. Interestingly, we have observed that liver-specific deletion of GR resulted in a significant increase in mRNA expression of key genes involved in gluconeogenesis and glycogen metabolism in kidney tissue, indicating a compensatory mechanism to maintain glucose homeostasis. We have also observed that GR plays an important role in regulating the mRNA expression of key genes involved in lipid metabolism. Liver GRKO mice demonstrated decreased fat mass and liver glycogen content compared with WT mice administered dexamethasone for 2 weeks. Adipose-specific deletion of GR did not alter glucose tolerance or insulin sensitivity of adipose GRKO mice compared with WT mice administrated dexamethasone. This indicates that liver GR might be more important in development of MS in dexamethasone-treated mice, whereas adipose GR plays a little role in these paradigms.
Studying the local solvent surrounding nanoparticles is important to understanding the energy exchange dynamics between the particles and their environment, and there is a need for spectroscopic ...methods that can dynamically probe the solvent region that is in nearby contact with the nanoparticles. In this work, we demonstrate the use of time-resolved infrared spectroscopy to track changes in a vibrational mode of local water on the time scale of hundreds of picoseconds, revealing the dynamics of heat transfer from gold nanorods to the local water environment. We applied this probe to a prototypical plasmonic photothermal system consisting of organic CTAB bilayer capped gold nanorods, as well as gold nanorods coated with varying thicknesses of inorganic mesoporous-silica. The heat transfer time constant of CTAB capped gold nanorods is about 350 ps and becomes faster with higher laser excitation power, eventually generating bubbles due to superheating in the local solvent. Silica coating of the nanorods slows down the heat transfer and suppresses the formation of superheated bubbles.
Berardinelli-Seip congenital generalized lipodystrophy is associated with increased bone mass suggesting that fat tissue regulates the skeleton. Because there is little mechanistic information ...regarding this issue, we generated "fat-free" (FF) mice completely lacking visible visceral, subcutaneous and brown fat. Due to robust osteoblastic activity, trabecular and cortical bone volume is markedly enhanced in these animals. FF mice, like Berardinelli-Seip patients, are diabetic but normalization of glucose tolerance and significant reduction in circulating insulin fails to alter their skeletal phenotype. Importantly, the skeletal phenotype of FF mice is completely rescued by transplantation of adipocyte precursors or white or brown fat depots, indicating that adipocyte derived products regulate bone mass. Confirming such is the case, transplantation of fat derived from adiponectin and leptin double knockout mice, unlike that obtained from their WT counterparts, fails to normalize FF bone. These observations suggest a paucity of leptin and adiponectin may contribute to the increased bone mass of Berardinelli-Seip patients.
Background
ATLS suggests simple thoracostomy (ST) after failure of needle thoracostomy (NT) in thoracic trauma. Some EMS agencies have adopted ST into their practice. We sought to describe our ...experience implementing ST in the prehospital setting, hypothesizing that prehospital ST would reduce failure rates and improve outcomes compared to NT.
Methods
This was a retrospective review of adult trauma patients who received prehospital ST or NT from 2017 to 2020.
Results
There were 48 patients with 64 procedures included. 83.7% were male and 65.8% injured by penetrating mechanism and of median (IQR) age of 31 (25-46) years. 28 (43.8%) procedures were NT and 36 (56.3%) were ST. Rates of improved patient response (P = .15), noted return of blood/air (P = .19), and return of spontaneous circulation (P = .62) did not differ. On-scene times were higher for ST (16.8 vs 11.5 minutes; P < .02). Overall mortality did not differ between ST and NT (68.2% vs 46.4%, respectively; P = .125). For patients that survived beyond the ED, procedure-related complication rates were 2 of 21 patients (9.5%) in ST and 1 of 12 (8.3%) in NT. In penetrating trauma, simple thoracostomy had longer on-scene time and total prehospital time.
Discussion
ST did not improve success rates of ROSC and was associated with prolonged prehospital times, especially in penetrating trauma patients. Given the benefit of “scoop and run” in urban penetrating trauma, consideration should be given to direct transport in lieu of ST. Use of ST in blunt trauma should be evaluated prospectively.
Osteoarthritis (OA), the leading cause of pain and disability worldwide, disproportionally affects individuals with obesity. The mechanisms by which obesity leads to the onset and progression of OA ...are unclear due to the complex interactions among the metabolic, biomechanical, and inflammatory factors that accompany increased adiposity. We used a murine preclinical model of lipodystrophy (LD) to examine the direct contribution of adipose tissue to OA. Knee joints of LD mice were protected from spontaneous or posttraumatic OA, on either a chow or high-fat diet, despite similar body weight and the presence of systemic inflammation. These findings indicate that adipose tissue itself plays a critical role in the pathophysiology of OA. Susceptibility to posttraumatic OA was reintroduced into LD mice using implantation of a small adipose tissue depot derived from wild-type animals or mouse embryonic fibroblasts that undergo spontaneous adipogenesis, implicating paracrine signaling from fat, rather than body weight, as a mediator of joint degeneration.
PDF
