Hundreds of millions of people are affected by hyperinsulinaemia, insulin resistance, obesity and the dysglycaemia that mark a common progression from metabolic health to type 2 diabetes. Although ...the relative contribution of these features and the order in which they appear may differ between individuals, the common clustering and seemingly progressive nature of type 2 diabetes aetiology has guided research and clinical practice in this area for decades. At the same time, lively debate around the causal relationships between these features has continued, as new data from human trials and highly controlled animal studies are presented. This ‘For debate’ article was prompted by the review in
Diabetologia
by Esser, Utzschneider and Kahn (
https://doi.org/10.1007/s00125-020-05245-x
), with the purpose of reviewing established and emerging data that provide insight into the relative contributions of hyperinsulinaemia and impaired glucose-stimulated insulin secretion in progressive stages between health, obesity and diabetes. It is concluded that these beta cell defects are not mutually exclusive and that they are both important, but at different stages.
Graphical abstract
Beginning with the simple question, "Why did audiences grow
silent?" Listening in Paris gives a spectator's-eye view
of opera and concert life from the Old Regime to the Romantic era,
describing the ...transformation in musical experience from social
event to profound aesthetic encounter. James H. Johnson recreates
the experience of audiences during these rich decades with brio and
wit. Woven into the narrative is an analysis of the political,
musical, and aesthetic factors that produced more engaged
listening. Johnson shows the gradual pacification of audiences from
loud and unruly listeners to the attentive public we know today.
Drawing from a wide range of sources-novels, memoirs, police files,
personal correspondence, newspaper reviews, architectural plans,
and the like-Johnson brings the performances to life: the hubbub of
eighteenth-century opera, the exuberance of Revolutionary
audiences, Napoleon's musical authoritarianism, the bourgeoisie's
polite consideration. He singles out the music of Gluck, Haydn,
Rossini, and Beethoven as especially important in forging new ways
of hearing. This book's theoretical edge will appeal to cultural
and intellectual historians in many fields and periods.
3D printing of fiber-reinforced thermoset composites is desirable for rapid fabrication of 3D composite objects with minimal tooling. One of the main issues in 3D printing of thermoset composites is ...the low cure rates of matrix resins, which prevents rapid curing and rigidization of composite materials during the printing process and capturing the desired print geometry. Here, we demonstrate a new technique for in situ printing and curing of carbon-fiber-reinforced thermoset composites without any postcuring or postprocessing steps. Upon extrusion and deposition of the composite ink from a printing nozzle, the ink is cured via frontal polymerization, leading to rapid printing of high-quality composites. Tailoring the processing conditions allows for freeform or rapid, supported printing of 3D composite objects with zero void content and highly oriented carbon fiber reinforcements.
Pragmatism and its consequences are central issues in American politics today, yet scholars rarely examine in detail the relationship between pragmatism and politics. In The Priority of Democracy, ...Jack Knight and James Johnson systematically explore the subject and make a strong case for adopting a pragmatist approach to democratic politics--and for giving priority to democracy in the process of selecting and reforming political institutions.
Escherichia coli sequence type 131 (ST131) is an extensively antimicrobial-resistant E. coli clonal group that has spread explosively throughout the world. Recent molecular epidemiologic and ...whole-genome phylogenetic studies have elucidated the fine clonal structure of ST131, which comprises multiple ST131 subclones with distinctive resistance profiles, including the (nested) H30, H30-R, and H30-Rx subclones. The most prevalent ST131 subclone, H30, arose from a single common fluoroquinolone (FQ)-susceptible ancestor containing allele 30 of fimH (type 1 fimbrial adhesin gene). An early H30 subclone member acquired FQ resistance and launched the rapid expansion of the resulting FQ-resistant subclone, H30-R. Subsequently, a member of H30-R acquired the CTX-M-15 extended-spectrum beta-lactamase and launched the rapid expansion of the CTX-M-15-containing subclone within H30-R, H30-Rx. Clonal expansion clearly is now the dominant mechanism for the rising prevalence of both FQ resistance and CTX-M-15 production in ST131 and in E. coli generally. Reasons for the successful dissemination and expansion of the key ST131 subclones remain undefined but may include increased transmissibility, greater ability to colonize and/or persist in the intestine or urinary tract, enhanced virulence, and more-extensive antimicrobial resistance compared to other E. coli. Here we discuss the epidemiology and molecular phylogeny of ST131 and its key subclones, possible mechanisms for their ecological success, implications of their widespread dissemination, and future research needs.
A systematic literature review and subsequent meta-analysis were performed to investigate differences in childhood obesity between urban and rural areas in the United States.
A search of published ...studies comparing childhood obesity in urban and rural settings was undertaken by probing PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) for articles that met predetermined inclusion criteria. A subsequent meta-analysis was conducted to determine the combined effect size and significance of differences in childhood obesity between urban and rural areas.
Ten studies were identified for systematic review, five of which contributed to the meta-analysis. All but one study suggested that residence in rural areas was associated with higher prevalence or increased odds of childhood obesity, compared to children living in urban areas. A meta-analysis of 74,168 pooled participants ages 2-19 found that rural children have 26% greater odds of obesity, compared to urban children (odds ratio=1.26; 95% confidence interval, 1.21-1.32).
Obesity rates are higher among rural children than urban children in the United States. To ensure successful targeted interventions and effective resource allocation, practitioners and policy makers alike should be cognizant of this disparity in childhood obesity.
Structures of riboswitch receptor domains bound to their effector have shown how messenger RNAs recognize diverse small molecules, but mechanistic details linking the structures to the regulation of ...gene expression remain elusive. To address this, here we solve crystal structures of two different classes of cobalamin (vitamin B(12))-binding riboswitches that include the structural switch of the downstream regulatory domain. These classes share a common cobalamin-binding core, but use distinct peripheral extensions to recognize different B(12) derivatives. In each case, recognition is accomplished through shape complementarity between the RNA and cobalamin, with relatively few hydrogen bonding interactions that typically govern RNA-small molecule recognition. We show that a composite cobalamin-RNA scaffold stabilizes an unusual long-range intramolecular kissing-loop interaction that controls mRNA expression. This is the first, to our knowledge, riboswitch crystal structure detailing how the receptor and regulatory domains communicate in a ligand-dependent fashion to regulate mRNA expression.
ABSTRACT
We investigate the impact of bursts in star formation on the predictions of one-zone chemical evolution models, adopting oxygen (O), iron (Fe), and strontium (Sr), as representative α, ...iron-peak, and s-process elements, respectively. To this end, we develop and make use of the Versatile Integrator for Chemical Evolution (VICE), a python package designed to handle flexible user-specified evolutionary parameters. Starbursts driven by a temporary boost of gas accretion rate create loops in O/Fe–Fe/H evolutionary tracks and a peak in the stellar O/Fe distribution at intermediate values. Bursts driven by a temporary boost of star formation efficiency have similar effects, and they also produce a population of α-deficient stars during the depressed star formation phase following the burst. This α-deficient population is more prominent if the outflow rate is tied to a time-averaged star formation rate (SFR) instead of the instantaneous SFR. Theoretical models of Sr production predict a strong metallicity dependence of supernova and asymptotic giant branch star yields, though comparison to data suggests an additional, nearly metallicity-independent source. Evolution of Sr/Fe and Sr/O during a starburst is complex because of this metallicity dependence and the multiple time-scales at play. Moderate amplitude (10–20 per cent) sinusoidal oscillations in SFR produce loops in O/Fe–Fe/H tracks and multiple peaks in O/Fe distributions, a potential source of intrinsic scatter in observed sequences. We investigate the impact of a factor ∼2 enhancement of Galactic star formation ∼2 Gyr ago, as suggested by some recent observations. VICE is publicly available at <http://pypi.org/project/vice/>.
The production of fully functional insulin-secreting cells to treat diabetes is a major goal of regenerative medicine. In this article, I review progress towards this goal over the last 15 years from ...the perspective of a beta cell biologist. I describe the current state-of-the-art, and speculate on the general approaches that will be required to identify and achieve our ultimate goal of producing functional beta cells. The need for deeper phenotyping of heterogeneous cultures of stem cell derived islet-like cells in parallel with a better understanding of the heterogeneity of the target cell type(s) is emphasised. This deep phenotyping should include high-throughput single-cell analysis, as well as comprehensive ’omics technologies to provide unbiased characterisation of cell products and human beta cells. There are justified calls for more detailed and well-powered studies of primary human pancreatic beta cell physiology, and I propose online databases of standardised human beta cell responses to physiological stimuli, including both functional and metabolomic/proteomic/transcriptomic profiles. With a concerted, community-wide effort, including both basic and applied scientists, beta cell replacement will become a clinical reality for patients with diabetes.
Extraintestinal pathogenic Escherichia coli (ExPEC) strains are important pathogens that cause diverse diseases in humans and poultry. Some E. coli isolates from chicken feces contain ...ExPEC-associated virulence genes, so appear potentially pathogenic; they conceivably could be transmitted to humans through handling and/or consumption of contaminated meat. However, the actual extraintestinal virulence potential of chicken-source fecal E. coli is poorly understood. Here, we assessed whether fecal E. coli isolates from healthy production chickens could cause diseases in a chicken model of avian colibacillosis and three rodent models of ExPEC-associated human infections. From 304 E. coli isolates from chicken fecal samples, 175 E. coli isolates were screened by PCR for virulence genes associated with human-source ExPEC or avian pathogenic E. coli (APEC), an ExPEC subset that causes extraintestinal infections in poultry. Selected isolates genetically identified as ExPEC and non-ExPEC isolates were assessed in vitro for virulence-associated phenotypes, and in vivo for disease-causing ability in animal models of colibacillosis, sepsis, meningitis, and urinary tract infection. Among the study isolates, 13% (40/304) were identified as ExPEC; the majority of these were classified as APEC and uropathogenic E. coli, but none as neonatal meningitis E. coli. Multiple chicken-source fecal ExPEC isolates resembled avian and human clinical ExPEC isolates in causing one or more ExPEC-associated illnesses in experimental animal infection models. Additionally, some isolates that were classified as non-ExPEC were able to cause ExPEC-associated illnesses in animal models, and thus future studies are needed to elucidate their mechanisms of virulence. These findings show that E. coli isolates from chicken feces contain ExPEC-associated genes, exhibit ExPEC-associated in vitro phenotypes, and can cause ExPEC-associated infections in animal models, and thus may pose a health threat to poultry and consumers.
PDF
